253 Matching Annotations
  1. Aug 2019
    1. postmitotic neurons

      Mature cells that are not capable of cell division.

      Question that is being addressed here is: Compared to immature/developing neurons, does mature cells have a different machinery (or set of mechanisms) to synthesize RNA and different neurotransmittters?

    2. inhibitory

      A neurotransmitter that has reduced effects on the neurons.

    3. membrane depolarization

      Refers to a process during which a cell undergoes a shift in electric charge distribution. At rest, the membrane of a neuron has a potential of -60 to -70 millivolts (mV). This means the inside of the cell is negatively charged relative to the outside. Depolarization is when the potential becomes less negative than the resting potential.

    4. tetrodotoxin, which prevents Na+ influx elicited by veratridine, prevented the effects of depolarization

      The sodium influx caused by veratridine was cancelled out by tetrodotoxin exposure. Tetrodotoxin blocks the influx of sodium ions thereby stopping depolarization. Hence there is no increase in the activity of substance P in the presence of both drugs.

    5. C. F. Dreyfus, K. A. Markey, M. Goldstein, I. B. Black, Dev. Biol. 97, 48 (1983)

      Dreyfus et al. used locus coeruleus, a region in the brain, to study neurotransmitter expression in brain. His group was able to show that the catecholamines can be expressed both in culture and in animals, making the locus coeruleus an excellent system to study the plasticity in brain.

    6. J. E. Adler and I. B. Black, Science, in press

      Given that the plasticity occurs during development, the authors tested whether the plasticity can be observed in mature neurons as well. The authors performed these experiments in the ganglia of young and old rats and assessed the changes in the neurotransmitter, substance P.

      Substance P had a significant increase in expression at young rats and at 6-month-old rats but not 2-year-old rats.

    7. G. M. Jonakait, K. A. Markey, M. Goldstein, I. B. Black, Dev. Biol. 101, 51 (1984)

      Jonakait et al. show that the loss of expression is not confined to the rat gut, but also observed in the cranial sensory and dorsal root ganglia of the embryonic rats. Here the authors have shown that the expression of catecholamine is lost for a certain time period during the development.

      These studies suggest that, irrespective of embryonic origin, the loss in expression of neurotransmitters, catecholamine, and noradrenergic occur during development.

    8. G. M. Jonakait, J. Wolf, P. Cochard, M. Goldstein, I. B. Black, ibid. 76, 4683 (1979)

      Jonakait et al. used the embryonic neural cells in the rat gut to understand the expression of noradrenergic cells.

      It was shown that these neural cells exhibit several characteristics of noradrenergic cells at embryonic stages. The authors wanted to know if there were a change in expression levels of noradrenergic during the development. For a certain time period during the development, the expression of noradrenergic is lost; however, the uptake system of norepinephrine is present and functional.

    9. P. H. Patterson, Annu. Rev. Neurosci. 1, 1 (1978)

      In this review, Patterson discusses how we can manipulate the neurons’ decision to produce certain chemicals by altering the environmental factors. This manipulation can be performed during development by changing the fluid or culture conditions in which the neurons are growing.

    10. T. Hokfelt, O. Johansson, A. Ljungdahl, J. M. Lundberg, M. Schultzberg, Nature (London) 238, 515 (1980)

      This review by T. Hökfelt et al. discusses the identification of new neurotransmitters that are peptidergic in nature. Peptidergic refers to the neurons that release small peptides as their neurotransmitters.

      The article provides a snapshot of peptidergic neurons identified in the nervous system, namely, the brain, spinal cord, and peripheral nervous system.

    11. neosynaptogenesis

      "Neo" meaning new, "synaptogenesis" referring to the formation of connections between neurons.

    12. transmitter mutability may constitute a unique mechanism underlying plasticity in the nervous system

      The tadpoles in these experiments tends to attach only to their kin.

      However, there is neurotransmitter phenotype change from one to another. The researchers have found a mechanism that helps in regulation of this neurotransmitter phenotype change. The release of the neurotransmitter caused the tadpoles to bond to those who were not biologically related to them. The switching affected the social bond formation in tadpoles.

      Read more at the Dana Foundation.

    13. veratridine did not significantly alter TH-positive cell number, suggesting that depolarization increased TH per neuron rather than increasing the number of neurons.

      What could have been the cause of the increase in TH activity? The answers could be one of the two options: An increase in the number of TH-positive neurons in the sample or an increase in the amount of TH per neuron.

      In other words, is it an individual neuron's effect or a collective effort of all neurons in the sample? To address this, the authors decided to measure the number of TH-positive cells in the control and veratridine-treated cultures.

      The results show that the there is no difference in the number of neurons between both groups. Based on that, they concluded there is an increase in the amount of TH per neuron individually but not in the total number of TH-positive neurons.

    14. depolarizing concentrations of K+ reproduced the effect of veratridine, suggesting that depolarization per se increased TH activity

      Potassium (K+) is used as a depolarizing agent in this study. The depolarization using potassium is expected to behave similarly to the effects observed with veratridine as both the chemicals increase the influx of sodium channels.

      The authors show that, in the presence of potassium, there is approximately a 35% increase in TH activity as compared to their controls.

    15. pontine

      Refers to the group of neurons present in the pons of the brain.

      The pons is a brain region that links the medulla and the mid-brain. It serves as a message station between several areas of the brain.

    16. this effect was blocked by tetrodotoxin

      Tetrodotoxin is a sodium channel blocker while veratridine does the opposite, it activates these channels causing an influx of sodium. Since these two drugs act in opposition to each other, we expect them to have no net effect in the cultures. And that’s what was observed in the cultures exposed to veratridine in the presence of tetrodotoxin (see TTX+Ver in Figure 4). There is no further effect in the TH activity as compared to their controls.

    17. Veratridine exposure significantly increased TH activity over cultures of the contralateral control locus

      Veratridine binds to the sodium channel binding site thereby increasing the flow of sodium ions into the cell. The authors have shown that, when the cultures are exposed to veratridine, there is approximately a 40% increase in the activity of tyrosine hydrolase (TH) compared to their controls. Controls are cultures that are not exposed to any drugs.

    18. one-way analysis of variance

      Used to compare average means of two or more samples.

      Here, the authors used this test to measure the activity of substance P across the following groups: (1) control, (2) in the presence of tetrodotoxin, (3) in the presence of veratridine, and (4) in the presence of tetrodotoxin and veratridine.

      Read more at Khan Academy.

    19. S.E.

      Stands for standard error, a measure to test how far the mean of the sample is from the estimated mean of the population.

    20. Control

      These are explants obtained from nucleus locus ceruleus. These explants are placed in a nutrient medium and no drugs are provided to this group. This group serve as a comparison group to the groups treated with the drugs.

    21. Autoradiography

      The last step in the dot blot to detect the materials of interest using a radioactive probe. Here, the radioactive probes tagged to proenkephalin were observed for three time points: 0 days, 1 day, and 3 days.

    22. The medullary explants exhibited a 50-fold rise in [Leu]enkephalin within 4 days, after a 2-day lag period, and continued increasing through 7 days, the longest time examined. In contrast, TH activity remained constant throughout, while PNMT decreased 60 percent in the first 4 hours, maintaining a stable plateau thereafter.

      Medullary explants were obtained from adult rats to understand the mechanism behind the different transmitter expression. 

      The tyrosine hydroxylase (TH) activity stayed consistent throughout the seven-day period. TH enzyme is responsible for the synthesis of catecholamines. The consistent TH activity indicates that there is no change related to the expression of catecholamines in this experiment. 

      Next, the PNMT enzyme is responsible for adrenergic expression. PMNT exhibited a 60% decrease in four hours and was maintained at that level for the remainder time period. 

      The [leu]enkephalin (opiate expression) showed a 50-fold increase in four days and continued to increase until seven days. There is a continuous increase in the expression of opiates as opposed to catecholamines.

    23. neural crest

      A structure that gives rise to the peripheral nervous system and non-neuronal cells.

    24. carotid body

      These bodies, consisting of receptors and cells, are located near the carotid arteries. There are two carotid arteries that run on either side of the neck, carrying blood to the neck, face, and brain.

    25. epibranchial placode

      A structure that gives rise to neurons and other structures in the nervous system.

      Learn more about placodes with another annotated paper: https://www.scienceintheclassroom.org/research-papers/hair-feathers-and-scales-evolutionary-tale

    26. immunocytochemical reactivity

      Technique used to mark the target of interest using an antibody-based test. In this study, tyrosine hydroxylase and dopamine β-hydroxylase are the target molecules of interest. The antibodies against tyrosine hydroxylase—namely dopamine β-hydroxylase—are used to detect the molecule of interest.

    27. Depolarization with veratridine completely blocked the increase of substance P

      Explants were depolarized with veratridine, leading to a decrease in the levels of substance P.

    28. In culture, the (now denervated) adult ganglia exhibited a tenfold rise in substance P, mimicking the increase in neonatal ganglia

      Explants from the superior cervical ganglia were obtained to address the question: Is there transmitter plasticity in mature neurons?

      Explants were obtained from rats of age six months and one year. A ten-fold increase was observed in the activity of substance P.

    29. explanted superior cervical ganglia

      The ganglia was removed from the animal and transferred to a nutrient medium. These explants were maintained in the medium for six months to one year. At several time points, the explants were taken and observed for the activity of substance P.

    30. in culture

      The neurons are dissected from the animal and grown in a dish. The dish contains supplemental factors and a medium that mimics the composition of the fluid inside the animal.

    31. phenotypic alteration may be mediated, at least in part, by specific hormones and alteration in the processing of specific species of mRNA

      The conversion of norepinephrine to epinephrine is dependent on the mRNA synthesis and hormones released by the pituitary-adrenal axis.

    32. transcriptional level

      A regulation that controls the conversion of DNA to RNA in organisms. Learn more with this HHMI BioInteractive video.

    33. regulation

      A set of codes that helps the organism adapt and maintain life.

      In this instance, regulation occurs at the gene level to adapt to environmental conditions.

    34. adrenal

      A gland situated above the kidneys. Adrenal glands produce a variety of hormones.

    35. neurohumoral products

      Neuroendocrine cells are the cells that receive input from neurons and release a hormone into blood for output. Any hormone produced and released by neuroendocrine cells are referred to as neurohumoral products.

    36. autonomic-adrenal axis

      Connections between the sympathetic nervous system and adrenal system.

    37. Consequently, these neurons may convert from catecholaminergic to cholinergic and peptidergic during development

      Neurons in rat sweat glands can convert from catecholaminergic to cholinergic groups during development. This is evident from the lack of enzymes that are responsible for catecholamine synthesis.

    38. VIP (vasoactive intestinal polypeptide)

      A neurotransmitter that can be released from exocrine glands; for instance, sweat glands.

      Functions include relaxation of smooth muscles in the stomach and gall bladder, and contraction of heart muscles.

      It has been shown that in sweat glands, both VIP and acetylcholine (or cholinergic) are released from the same population of neurons.

    39. dopamine-β-hydroxylase

      An enzyme that converts dihydroxyphenylalanine (DOPA) to dopamine.

    40. Consequently, neurons may respond to environmental information by altering transmitter phenotypic expression and, presumably, the signals sent to other neurons.

      Since this paper was published in 1984, the field of synaptic plasticity has progressed. This NeuWire article is an example to show that, in response to environmental conditions (such as changes in day length), the brain can switch the neurotransmitters they produce and release. These neurotransmitter switches also have an impact on behavior in these animals.

      See the original research in Science in the "Related Content" tab and here.

    41. may change transmitter status during development and maturity, upsetting the tacitly assumed dogma of transmitter immutability, and adding an entirely new dimension to our appreciation of neural plasticity.

      When this paper was published, it was assumed that each neuron produces only one transmitter. However, more recent research has challenged this assertion. Contrary to traditional teaching, this article summarizes the new findings in the field of neurotransmitter plasticity, some of which include mechanisms of neurotransmitter plasticity, mechanisms of neurotransmitter switching, and their impact in neurological disorders.

      Read more here.

    42. neurotransmitter plasticity.

      Plasticity can be defined as the ability of the brain to mold and shape in response to experience. The change can be due to change in the receptors present in the brain, the chemicals itself, or the mechanism by which receptors respond to chemicals. 

      Neurotransmitter plasticity refers to changes in neurotransmitters in response to plasticity.

    43. in vivo

      Experiments that are performed on animals or humans.

    44. vegetative functions

      Functions of the body that are essential for life; e.g., sleeping, eating, breathing, bladder activity.

    45. sympathetic neurons

      The sympathetic nervous system is a part of the nervous system that controls the essential functions of life; for example, blood pressure and heart rate. The neurons present in this system are called sympathetic neurons.

    46. nervous system

      You can think of the nervous system as electrical wiring, transmitting signals to and from different parts of the body. The system is made up of the brain, spinal cord, and nerves. Neurons are cells found in the brain.

    47. peripheral nervous system

      The human nervous system is made up of two components, the central nervous system (CNS) and the peripheral nervous system (PNS). The PNS consists of nerves and fibers outside of the brain and spinal cord (which make up the CNS).

    48. peptide transmitters

      These are a class of neurotransmitters. Peptides are made of amino acids or a chain of amino acids.

      Read more about the different neurotransmitters here.

    49. cholinergic

      Refers to the cells that release neurotransmitter acetylcholine.

      Learn more in this video about neurotransmitter release: https://www.khanacademy.org/science/health-and-medicine/nervous-system-and-sensory-infor/neural-cells-and-neurotransmitters/v/neurotransmitter-release

    50. noradrenergic

      Refers to cells that release the neurotransmitter, norepinephrine. An alternative name for norepinephrine is noradrenalin.

  2. Jun 2019
    1. J. A. Kessler, J. E. Adler, M. C. Bohn, I. B. Black, Science 214, 335 (1981); J. A. Kessler, J. E. Adler, W. O. Bell, I. B. Black, Neuroscience 9, 309 (1983)

      In these studies, the authors examined the role of the neurotransmitter substance P in nerve ganglia. The authors confirmed that the activity of substance P is dependent on sodium currents, changes within the cell, and impulsive activity.

    2. Axotomy of the petrosal neurons, separating the cell bodies from peripheral targets, resulted in a precipitous decline in TH catalytic activity and disappearance of TH immunoreactivity

      Cutting down the axons in the petrosal neurons causes a decrease in TH activity and immunoreactivity. However, there is a certain level of TH recovery after four weeks, which could be due to the regeneration or recovery of the severed axon.

    3. nicotinic receptor stimulation, with consequent depolarization or attendant transmembrane Na+ influx, or both, decrease substance P in mature sympathetic neurons, as in neonatal neurons

      With nicotinic receptor stimulation, the depolarization or the influx of sodium ions across the membrane causes a decrease in substance P in both mature and developing neurons.

    4. chlorisondamine

      A drug that blocks the binding of acetylcholine to its nicotinic receptors.

    5. neurogenesis

      Formation of new neurons.

    6. autoreceptors

      Referring to a case where the neurotransmitter and the receptors are present on the same cell. The released neurotransmitter binds to the receptor on the same cell.

    7. morphometric analysis

      A quantitative measurement of a neuron size, shape, or density.

    8. veratridine depolarization

      Veratridine is a drug that causes an increase in the sodium influx. The authors used the drug to cause depolarization.

    9. These observations suggest that membrane depolarization and associated transmembrane Na+ influx decrease [Leu]enkephalin in adult medulla

      Decrease in [leu]enkephalin in adrenal medulla is dependent on two related factors: Membrane depolarization and the sodium influx through the membranes.

    10. In contrast, 4-day adult explants revealed a marked increase in proenkephalin mRNA, which paralleled the rise in [Leu]enkephalin

      At four days, mRNA of proenkephalin showed a greater increase similar to the increase observed in [leu]enkephalin in medullary explants.

    11. histofluorescence

      Fluorescent markers are used to label catecholamine in the neurons and visualized using a fluorescent microscopy.

    12. unmanipulated

      No change; unaltered.

    13. nicotinic receptors

      These are receptors that respond to the neurotransmitter, acetylcholine.

    14. a ganglionic blocking agent that prevents depolarization by competing with acetylcholine for postsynaptic nicotinic receptors, reproduced the effects of denervation

      Using a blocking agent for nicotinic receptors, the binding of acetylcholine was blocked in the ganglia. This manipulation is similar to denervation technique and hence, the authors observed an increase in the activity of substance P.

    15. pituitary-adrenal axis

      Refers to the connections and interactions between the pituitary gland and adrenal glands. 

    16. progenitors


    17. tetrodotoxin

      Sodium channel blocker. It blocks the influx of sodium into the cell.

    18. influx

      Act of flowing in.

      Example: An influx of tourists was observed over the holidays.

    19. catecholaminergic

      Refers to the cell group that releases one of the neurotransmitters, dopamine or norepinephrine.

    20. tyrosine hydroxylase

      An enzyme responsible for the conversion of tyrosine (an amino acid) to dopamine, a neurotransmitter.

    21. the high-affinity uptake system for α-CH3-norepinephrine (5), a characteristic of noradrenergic neurons

      The uptake of norepinephrine in these neurons remain unaffected. The neurons are capable of producing noradrenaline.

    22. Sympathetic neurons innervating rat eccrine sweat glands appear to convert from noradrenergic to cholinergic

      Noradrenergic neurons produce norepinephrine, the neurotransmitter expressed in rat sweat glands during postnatal stages of development. For a short period of time in development, the neurons lose the noradrenergic expression, but pick up the expression of acetylcholine.

    23. quantitative

      Refers to the measurement of quantities, a countable amount of something. For example: A baby weighs 7 pounds and 4 ounces.

    24. qualitative

      Refers to the measurement of qualities, a describable trait of something. For example: The girl has brown eyes.

    25. phenotype

      Here, referring to the physical characteristics of the neurons.

    26. peptide putative transmitters

      Widely accepted class of neurotransmitters.

      Read more about the different neurotransmitters here.

    27. Neurotransmitters

      A chemical that is released by brain cells called neurons. These chemicals aid in communication or passing messages between neurons.

    28. veratridine

      Drug that increases the influx of sodium into the cell.

    29. mutability

      The ability to change.

      For example, think of a caterpillar, which has the ability to change to butterfly.

    30. thermoregulation

      Maintaining the body’s temperature within the normal limits.

    31. basal

      Normal or minimum level.

    1. translational

      Research that can be useful to prevent or treat disease

    2. developmental

      Relating to the growth of the individual.

    3. subsequent


    4. cocaine-induced

      The response prompted by cocaine.

    5. nicotine-induced

      Response prompted by nicotine.

    6. risk

      Prone to; susceptible.

    7. pretreatment

      Treatment received prior to something in advance

    8. assessed

      Evaluate; measure.

    9. administered


    10. prompted

      Pushed; urged; required.

    11. diminished


    12. Locomotor sensitization

      A technique used to measure the movement or locomotor activity of the animal assessed in the open field box. It is thought that with repeated administration of the drug, the animals can show an increase in locomotor activity, which is a sign of sensitization.

      Photobeams are placed on the walls of the box to record the movements of the animal. The mice can explore and get used to the test area of the open field.

      The animal is tracked for the distance covered in centimeters using an automated video system. The experiment is repeated on day 1 and on each day following the injection of cocaine (on days 8, 9, 10, 11). The total distance covered by the animal is recorded for each day.

      Watch the technique here at: https://www.jove.com/video/53107/assessment-cocaine-induced-behavioral-sensitization-conditioned-place

    13. CPP measures an animal’s preference for a particular place in its environment, which develops as that place becomes consistently associated with a rewarding stimulus and assumes some of the rewarding effects of the stimulus

      A three-chamber apparatus is constructed with access to two chambers for the animal for this experiment. There are 3 phases to this experiment: pre-conditioning, conditioning, and testing.

      Pre-conditioning: Animal can freely move on any side of the chamber. For each animal, the first preference of the chamber is noted. This was done on days 7 and 8 of the experimental protocol.

      Conditioning: Train the animals to saline on its preferred chamber and to cocaine on the least preferred side. This was done on days 9, 10, and 11 of the experimental protocol.

      Testing: On day 12 of the experiment, the animals are allowed to have access to both sides of the chamber for 30 minutes. The time spent in the preferred chamber and the less preferred chamber is recorded.

      View the video to learn more about the conditioned place preference protocol. The protocol is describing how to measure craving in animals using morphine as the drug of preference. https://www.jove.com/video/58384/a-conditioned-place-preference-protocol-for-measuring-incubation

    14. endpoints


    15. long-term synaptic potentiation

      Strengthening of synapses between neurons

    16. long-term potentiation

      Slice electrophysiology is a technique that is widely used to study synaptic plasticity. Brain slices containing the nucleus accumbens region was obtained from the mice.

      For this technique, stimulating and recording electrodes are needed. Recording electrodes measure the electrical activity of the neurons in the area. Stimulating electrodes are used to stimulate a dendrite (s) in the brain region that can elicit a response which can be recorded via the recording electrode. The stimulus is given at a rate of 1 per minute.

      The stimulating electrode was placed in the nucleus accumbens, and the recording electrode was placed near to the stimulating electrodes.

      The amplitude or the size of the response can be calculated from each stimulus. Baseline values were obtained. After that, an LTP stimulus was given, and the post-LTP data was collected. The data were normalized to baseline values.

      Watch the video here on LTP is done in hippocampus, a brain region involved in memory: https://www.jove.com/video/2330/preparation-acute-hippocampal-slices-from-rats-transgenic-mice-for

    17. high-frequency stimulation

      The neurons are activated by a high frequency of 100Hz. The protocol used here: 4 trains of 100 Hz tetanus 3 mins apart and are represented below:

    18. FosB expression

      Chromatin immunoprecipitation technique is used to measure FosB expression.

      Briefly, the brain tissue was fixed with formaldehyde to crosslink the DNA binding proteins. The DNA was sheared into small fragments, some of which contains the DNA binding proteins. Using specific antibodies (H4, H3), the DNA binding protein complex was isolated. The proteins are digested, and the DNA is released. The specific DNA sequences of interest were amplified to see if they precipitated with the antibody.

      Watch the video here: https://www.jove.com/science-education/5551/chromatin-immunoprecipitation

    19. PCR

      mRNA was isolated from the brain tissue using the Trizol reagent. RNA was later reverse transcribed to cDNA or complementary DNA using primers of interest. The fold difference of mRNA over control values is calculated and compared across the groups.

      Check the video here on the technique: https://www.youtube.com/watch?v=0MJIbrS4fbQ

    20. Immunoblots

      Protein was extracted from the tissue. Proteins are separated based on molecular weights in a SDS-Page gel. The gel was transferred to nitrocellulose membrane.

      The antibodies to H3 and H4 were applied to the membrane to detect the bands of interest.

      Watch the technique here: https://www.jove.com/science-education/5065/the-western-blot

    21. SAHA

      The drug was administered directly to the nucleus accumbens of the mice.

      In order to do so, the coordinates of the nucleus accumbens are obtained from the mouse brain atlas. The mouse is placed in a stereotaxic chamber, and the cannula was inserted into the brain to inject the drug every day for 7 days. The cannula was guided to be inserted into the brain using the coordinates

    22. HDAC activity

      The nuclear fractions are obtained from the mice using a nuclear extraction kit. HDAC activity was measured using the kit.

    23. prenatal

      before birth; during pregnancy

    24. phenocopied

      mimicked; acted similarly

    25. transient

      only for a short time

    26. baseline


    27. facilitation

      help; make the process easy

    28. variant


    29. ERK/MAPK

      signaling pathways that help in gene regulation

    30. phosphorylates

      adding phosphate residues

    31. concurrent

      happening at the same time

    32. Hypoacetylated

      not enough acetylation

    33. deacetylase

      removal of acetyl groups

    34. hyperacetylation

      increase or excessive acetylation

    35. promoter

      DNA sequences that define where the transcription should start in a gene

    36. disinhibits


    37. simulate

      prompt or trigger

    38. psychostimulants

      drugs that cause an increased behavioral or motor response

    39. robust

      widely used

    40. behavioral paradigm

      a model designed to perform behavioral experiments

    41. acetylation

      Process by which acetyl groups are added to preferred residues in a protein.

      For instance, acetyl groups are added to lysine residues in a protein structure

    42. histone

      components of chromatin that helps in gene regulation

    43. chromatin

      DNA + histone

    44. FosB

      it is one of the transcription factors that help in gene expression

    45. transcription

      the process by which a copy of genetic information is made from DNA to RNA

    46. synaptic

      A synapse is a space between the neurons that allows passage of electric or chemical signals between the neurons.

      Anything that occurs between synapses is referred to as synaptic

    47. plasticity

      the ability of the neurons (brain cells) to change and learn new things by changing their synaptic strength

    48. spiny neurons

      Medium sized neurons that have dendritic branches

    49. inhibitory

      slowing down, hold back, restrain, negatively affecting a response

    50. GABAergic

      neurons that contain inhibitory neurotransmitter, GABA

    51. prefrontal cortex

      Part of the frontal cortex in the brain. Its function includes planning, organization, and decision making

    52. amygdala

      A brain region present in the temporal lobe. It is almond In shape. It plays an important role in emotions.

      Eg. When we see a lion, we immediately run due to fear. The fear response is due to the amygdala.

    53. ventral tegmental area

      A brain region in the midbrain. Serves as a center for the origin of dopaminergic neurons

    54. glutamatergic

      neurons that can modulate (or alter or modify) the neurotransmitter, glutamate. Glutamate is an excitatory neurotransmitter

    55. dopaminergic

      neurons that contain neurotransmitter, dopamine. Dopamine plays a vital role in the reward pathway

    56. integration

      to combine the similarities together

    57. convergence

      bringing together two different concepts that share similarities

    58. reward

      recognition of one’s work or effort

    59. ventral striatum

      contains the brain region, nucleus accumbens

    60. nucleus accumbens

      A brain region in the forebrain. It has two parts: core and shell

    61. addictive

      causing someone to become dependent

    62. cocaine

      Recreational drug. Referred as coke.

    63. nicotine

      primary chemical present in tobacco

    64. addiction

      dependency, craving

    65. modulated


    66. enhanced


    67. place preference

      preferred choice of one place over another

    68. conditioned

      trained or habituated

    69. sensitization

      Repeated administration of a stimulus can cause a response to the stimulus.

      Eg. If you give your cat piping hot milk the first day, the cat may not drink it as it will burn its mouth. However, if you continue to give your cat hot milk for several days in a row, the cat will eventually start drinking the milk as it is habituated to the new stimulus (hot milk) and will not complain

    70. Locomotor

      the movement of a living being from one place to another

    71. sequential

      one by one; logical order

    72. determinant

      a key factor

    73. irrelevant

      not important

    74. molecular genetic

      study of the structure and function of genes involved in the behavior

    75. electrophysiological

      observing the electrical properties of neurons in the mouse brain

    76. behavioral

      observing the behavior of the mouse

    77. exert


    78. gateway drugs

      the substances are mild and not addictive on consumption. However, the continuous consumption of these mild substances can lead to the use of other addictive drugs. They are also known as ‘habit-forming drug.’

      Eg. Alcohol, Cigarettes.

    79. epidemiological

      Deals with incidence and distribution of diseases and societal issues

    80. illicit drug

      Substances that are addictive to the central nervous system.

      These substances are illegal to be possessed, have no documented therapeutic effect, and are referred to as drugs of abuse.

      Eg. Cocaine, Heroin

    81. marijuana

      ‘weed’ or ‘pot.’

      Read more about marijuana here: https://www.drugabuse.gov/publications/research-reports/marijuana/what-marijuana

    82. Similarly, the expression of FosB after cocaine administration was the same in mice exposed to nicotine 14 days earlier and in mice without previous nicotine exposure

      In contrast to the results we obtained with 7 days of nicotine treatment paired with cocaine, these animals did not show any change in the magnitude of LTP, no increase in locomotor activity of in FosB gene expression.

      This indicates that the priming effect of nicotine can occur only when the drugs are given in a close window and not otherwise.

    83. 14 days after stopping 7 days of nicotine treatment

      The mice receive 7 days of nicotine or water, and then the animals are weaned off the drug for 14 days. Cocaine was administered to animals after day 14 of treatment.

    84. To investigate further the duration of the priming effect of nicotine

      What is the duration of nicotine exposure that is needed to obtain the priming response we see in these animals?

      Does nicotine need to be given closer to another drug or separated a few days apart?

    85. Theophylline-treated mice also showed a reduction in levels of acetylated histone H4

      A reduction in acetylated levels of histone H4 was observed

    86. The acetylated chromatin induced by nicotine exposure would then allow greater FosB gene expression in response to cocaine injection than FosB gene expression after cocaine alone.

      Figures 5 and 6 suggest that the nicotine inhibits HDAC activity, thereby causing global acetylation in the striatum and affecting gene expression.

      In response to cocaine, this acetylation is further enhanced, thus allowing a more significant response in gene expression.

    87. exhibited no increase in FosB mRNA expression in response to cocaine, although cocaine alone increased FosB expression by 176%

      FosB gene expression is also reduced in mice treated with theophylline and cocaine compared to theophylline alone.

    88. Both groups showed a comparable increase in LTP. However, the theophylline-treated mice exhibited an attenuated LTP reduction in response to cocaine treatment

      As expected, in LTP experiments, the mice treated with theophylline and cocaine injections showed a decrease in the magnitude of LTP compared to mice treated with theophylline alone.

    89. To test further the idea that histone acetylation and deacetylation are key molecular mechanisms for the effect of nicotine on the response to cocaine, we conducted two sets of experiments, one genetic and one pharmacological

      Next, the authors tested the idea of histone acetylation by using a low dosage of theophylline, an HDAC stimulator. In contrast to SAHA, the theophylline should decrease the response to cocaine.

    90. Similar to nicotine alone, SAHA alone did not cause a depression in LTP

      SAHA alone did not impair LTP just like nicotine did not impair LTP.

    91. SAHA pretreatment fully simulated nicotine pretreatment and induced a greater reduction in LTP in the core of the NAc than did cocaine alone

      Pretreatment with SAHA followed by cocaine caused a dramatic decrease in the magnitude of LTP response at 180 mins. These results suggest that nicotine does inhibit HDAC activity.

    92. we found that a single cocaine injection after local pretreatment with SAHA for 7 days resulted in 142% more FosB mRNA expression than without pretreatment with SAHA

      Further, when SAHA was infused into nuclear accumbens for 7 days followed by cocaine injection, the FosB expression levels and acetylation of histone residues in striatum increased than the pretreatment with SAHA.

    93. observed a 71% increase in FosB expression in the pretreated mice compared to mice treated with cocaine alone

      Similar to nicotine, SAHA increased the FosB expression levels by 71% and caused acetylation of histone residues in the striatum.

    94. we asked whether we could simulate the effect of nicotine by specifically inhibiting deacetylases with the HDAC inhibitor suberoylanilide hydroxamine acid

      If nicotine is inhibiting HDAC activity, then by using an HDAC inhibitor, we should be able to mimic the effects of nicotine on LTP and FosB expression. This hypothesis was tested by using SAHA, an HDAC inhibitor.

    95. there was a 28% reduction in HDAC of mice treated for 7 to 10 days with nicotine

      28% reduction in HDAC activity was measured in animals treated with nicotine, suggesting that the nicotine inhibits the HDAC activity, thereby decreasing deacetylase activity.

    96. histone deacetylase (HDAC) activity directly in the nuclear fraction of cells in the striatum

      To confirm that, histone deacetylase activity (HDAC) was measured in the striatum.

    97. Does the hyperacetylation produced by nicotine result from activation of one or more acetylases or from the inhibition of deacetylases?

      The authors next addressed whether the acetylation of residues is due to an increase in activation of acetylases or due to inhibition of deacetylase.

    98. 7 days of nicotine treatment (10 μg/ml) increased histone H3 and H4 acetylation by 32 and 61% in the whole striatum, compared with controls treated with water, much as it did at the FosB promoter

      Again, there was an increase in acetylation levels of H3 and H4 in the striatum.

      These results suggest that the nicotine increases the effect of cocaine on FosB expression by increasing the acetylated residues in FosB, thereby enhancing chromatin reorganization.

    99. we used immunoblotting and examined the extent of chromatin modifications in the whole striatum of mice chronically treated with nicotine

      The authors observed the acetylation levels of H3 and H4 after 7 days of nicotine treatment in striatum tissue using chromatin immunoprecipitation and immunoblotting.

    100. We found that, after 7 days of nicotine treatment (10 μg/ml), acetylation of both histone H3 and histone H4 was increased by 34 and 39%, respectively

      Authors observed the acetylation of histone H3 and H4. It is shown that both H3 and H4 got acetylated after a single dose of cocaine injection and after nicotine pretreatment.

    101. whether nicotine enhances FosB expression in the striatum by altering chromatin structure at the FosB promoter and, if so, does it magnify the effect of cocaine?

      The authors asked the question: does nicotine increase FosB expression by altering the chromatin structure at FosB promoter?

    102. The effects on FosB expression are unidirectional; nicotine primes the cocaine response, but cocaine does not prime the nicotine response

      This suggests that the nicotine precedes cocaine and not in the reverse order.

    103. We found that 7 days of cocaine treatment blunted rather than amplified the effect of nicotine on FosB expression in the striatum when compared to the response to nicotine alone.

      On the contrary, the increase in FosB expression we observed in nicotine pretreatment is entirely absent with the cocaine pretreated animals.

    104. we gave cocaine (30 mg/kg) in two protocols: for 24 hours or 7 consecutive days followed by 24 hours of treatment with nicotine

      The animals were given cocaine in drinking water for 7 days. Later, the mice were administered nicotine for 4 days. FosB mRNA levels were measured.

    105. does nicotine pretreatment followed by cocaine increase the response to cocaine, whereas the reverse order of drug treatment does not?

      These experiments were performed to determine if the nicotine pretreatment combined with cocaine injection produces similar results to cocaine pretreatment combined with nicotine injection.

    106. Chronic nicotine administration produces changes in gene expression in the brain so that, after nicotine, the brain responds differently to cocaine with respect to long-term synaptic changes

      It could be that the nicotine causes a gene expression in animals. This primed response serves as a precursor for the brain to respond differently to cocaine to produce long term plasticity changes.

    107. As in the behavioral and physiological experiments, 24 hours of nicotine pretreatment produced quite different results from the 7-day treatment and did not lead to an increased FosB response to cocaine

      On the contrary, FosB expression was increased only in animals that received a cocaine injection after 7 days of nicotine treatment and not in 24 hours of treatment.

      This suggests that the long term nicotine effect is responsible for the changes in gene expression.

    108. we found that both 24 hours and 7 days of administration of nicotine (10 μg/mg) in the drinking water caused 50 and 61% increases in FosB expression

      Both 24 hours and 7 days of nicotine administration caused an increase in FosB expression by 50% and 61%.

    109. Treatment with cocaine alone for 7 days or cocaine treatment for 7 days followed by 24 hours of nicotine treatment did not alter LTP

      However, mice treated with cocaine show a 17% decrease in the observed LTP.

    110. The reduction started immediately after the high-frequency stimulation (HFS) and persisted for up to 180 min compared with cocaine alone

      In this experiment, the authors wanted to determine if the sequential drug use of cocaine can alter the cocaine-induced synaptic plasticity.

      After high-frequency stimulation (HFS), mice treated with nicotine alone or water exhibit LTP that lasts for 180 mins. Mice pretreated with nicotine combined with cocaine injection show a dramatic reduction (~40%) in the observed LTP.

      This suggests that the changes in LTP in nucleus accumbens is caused by pre-exposure of nicotine to the mouse.

    111. In brain slices taken from the striatum, we measured LTP in the excitatory synapses (in the cortico-accumbens pathway) in the NAc core (Fig. 2A), known to be reduced in response to chronic cocaine administration

      Cocaine is capable of producing LTP in several brain regions.

    112. We found that the rate of cocaine dependence was the highest among cocaine users who initiated cocaine after having smoked cigarettes

      Similar to the results obtained from animals, the individuals who started using cocaine were also active smokers, i.e., they initiated cocaine after smoking.

    113. mice pretreated with nicotine showed a 78% further increase in preference for the cocaine-coupled chamber compared with mice treated only with cocaine, with no previous exposure to nicotine

      Mice pretreated with nicotine coupled with cocaine injections showed a further 78% increase in preference to cocaine-coupled chamber than cocaine-treated animals.

      This suggests that persistent treatment of nicotine for 7 days increases the locomotor activity and behavioral responses of the animals

    114. Cocaine alone increased place preference by 223% compared with saline control

      The experiment was performed to determine the behavioral response in the 4 groups of animals.

      Do these animals have a conditioned place preference or aversion to cocaine? If the place preference to cocaine exists, which group out of 4 show the most sensitization to the CPP?

      In the conditioned place preference test, mice pretreated with cocaine alone showed preference to the cocaine-coupled chamber by 223%.

    115. Mice treated with nicotine for 7 days followed by cocaine showed a significant enhancement of 98% in locomotor activity compared with mice treated with cocaine alone

      Mice treated with nicotine for 7 days, followed by cocaine for 4 days show a 98% increase in locomotor activity than the control mice

    116. Mice treated only with cocaine showed a 58% increase in locomotion (sensitization) compared with controls

      Mice treated with an injection of cocaine for 4 days show a 58% increase in locomotor activity than the control mice

    117. Mice treated with nicotine (50 μg/ml) showed the same levels of locomotion (that is, no increase in locomotion compared to day 1) as water controls.

      There is no difference in the distance traveled by the animals that were treated with nicotine in drinking water versus drinking water. (yellow vs. black bars, fig 1A).

    118. We treated mice with nicotine (50 μg/ml) in the drinking water for either 24 hours (Fig. 1A) or 7 days

      Nicotine was added to the drinking water for the mice.

      7 days treatment: The mice were fed with the nicotine-containing water for 7 days. For the next 4 days, mice received a cocaine injection intraperitoneally (injection into a body cavity) with continuous exposure to nicotine-containing water. The injections were given once per day.

      24 hours of treatment. The mice were exposed to the nicotine-containing water for 24 hours, and the next 4 days; the mice received a cocaine injection (once per day) intraperitoneally with continuous exposure to nicotine-containing water.

    119. This result is consistent with our earlier finding that SAHA caused a marked increase in FosB expression when given before an acute cocaine injection compared with the effect of cocaine alone

      Similar to nicotine, SAHA also causes an increase in the expression levels of FosB