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Neuroscience of LearningAn Introduction toMind, Brain, Health, and EducationSection: NeurotransmittersHarvard University Extension School (PSYCE-1609)February 2, 2016Spring, 20161
Spring, 20162
Spring, 20163
Which of these is a neuron?Spring, 20164
Which of these is a neuron?All of them!Spring, 20165
What is the neuron doctrine?Spring, 20166
The Neuron DoctrineSantiago Ramon y CajalChick cerebellum neurons drawing by Ramon y Cajal (1905)Key tenet: Neurons are specialized brain cells that are notcontinuous, but contiguous (e.g., there is a gap/transmissionbarrier between neurons)2Spring, 20167
Neurons connect via a synapseSpring, 20168
Where’s the synapse?Spring, 20169
Where’s the synapse?Spring, 201610
Name that anatomy Spring, 201611
Name that anatomy Axonal bouton Pre-synaptic terminalSpring, 201612
Name that anatomy Spring, 201613
Name that anatomy Dendrite Post-synaptic terminalSpring, 201614
Name that anatomy Spring, 201615
Name that anatomy Synaptic VesiclesSpring, 201616
What’s inside synaptic vesicles?Synaptic VesiclesSpring, 201617
NeurotransmittersSpring, 201618
Are we making new vesicles all the time?Spring, 201619
Synaptic vesicles are constantly emptied,recycled, and refilledSpring, 201620
Where does all the NT go?Spring, 201621
Reuptake, Diffusion, MetabolismA lot of NTs aretaken back intothe vesicles forreuseSome breakdownSome diffuseSpring, 201622
How do neurons “fire?”Spring, 201623
Triggering an Action Potential FiringDendrites are “triggered” by aneighboring axonSpring, 201624
Triggering an Action Potential FiringThe cell body collects all thetriggers from the dendritesDendrites are “triggered” by aneighboring axonSpring, 201625
Triggering an Action Potential FiringAxon HillockThe cell body collects all thetriggers from the dendritesDendrites are “triggered” by aneighboring axonSpring, 2016If enough input is collected, thecell body triggers the axon totransmit the signal to allconnected neurons26
How does summation happen? Why does itneed to?Spring, 201627
Because neurons receive both excitatory andinhibitory inputSpring, ogy.com/vs03.html28
What is the end result of a neuron firing?Spring, 201629
What is the end result of a neuron firing?Neurotransmitter releaseSpring, 201630
Ionotropic: NT binds to the ion channelSpring, 201631
Metabotropic: NT binding opens ion channelsSpring, 201632
How much is being released? All of the vesicles within aneuron contain about thesame amount of NTSpring, 201633
How much is being released? All of the vesicles within aneuron contain about thesame amount of NT CNS synapses typicallyrelease one vesicle peraction potentialSpring, 201634
How much is being released? All of the vesicles within aneuron contain about thesame amount of NT CNS synapses typicallyrelease one vesicle peraction potential Neuromuscular synapsesrelease about 200 vesiclesper action potentialSpring, 201635
How much is being released?Why do muscles get more?Spring, 201636
How much is being released?Why do muscles get more?As a fail-safe to make suremuscles can contractSpring, 201637
Poll: What influences NT levels?Spring, 201638
Neurotransmitters have different jobsSpring, 201639
What if blocking a certain neurotransmittercaused muscle paralysis? What would youguess about it’s function?Spring, 201640
Botulism: Acetylcholine vesicles can’t m causes paralysisbecause it prevents therelease of acetylcholine(necessary for musclecontraction)Spring, 201641
Acetylcholine (excitatory) Stimulates muscle contraction Stimulates release of some hormones Helps regulate lots of things including: Spring, exual driveThirstLearning/memory42
Acetylcholine (excitatory) Alcohol decreases acetylcholine transmissionSpring, 201643
What if blocking a certain neurotransmittercaused muscle spasms? What would youguess about it’s function?Spring, 201644
Tetanus: GABA vesicles can’t releaseTetanus causes muscle spasm becauseit prevents the release of GABA whichinhibits muscular contraction themuscles never stop contractingMuscle spasms in a person with tetanus.Painting by Sir Charles Bell, 1809. Retrievedfrom https://en.wikipedia.org/wiki/TetanusSpring, 201645
GABA (inhibitory) Works throughout the brain to balance excitatory NTsooAbout 40% of neurons have GABA receptorsMost active inhibitory NT Synthesized from glutamate (the major excitatory NT) Essential for:oooSpring, 2016Motor control (refines movement)VisionAnxiety regulation46
What would happen to GABA levels ifglutamate levels decreased?Spring, 201647
What would happen to GABA levels ifglutamate levels decreased?They would decreaseSpring, 201648
Neurotransmitters influence each otherSpring, 201649
If you alter the levels of one, the others willadjust in responseNeurotransmitter MobileSpring, 201650
If you alter the levels of one, the others willadjust in responseNeurotransmitter MobileSpring, 201651
If you alter the levels of one, the others willadjust in responseNeurotransmitter MobileSpring, 201652
Glutamate (excitatory) Works throughout the brain Involved in most cognitivefunctions, especiallylearning and memory Critical agent for long-termpotentiation (Hebbianlearning)Spring, 2016Vance (2014)53
Glutamate (excitatory) Actions (at NMDA glutaminergicreceptors) can be blocked byalcoholSpring, 2016Vance (2014)54
Glutamate (excitatory) Actions (at NMDA glutaminergicreceptors) can be blocked byalcohol St. John’s Wort can increasereleaseSpring, 2016Vance (2014)55
If you want to learn better, should you takelots of St. John’s Wort so you increase yourglutamate levels?Spring, 201656
Too much glutamate is a bad thingSpring, nerative-disease-and-dementia/deck/142745905757
Do genes influence NT levels?Spring, 201658
Genes can influence NT levels/processing ADHD gene reduces dopamine release in dorsal striatum Gene associated with depression and suicide decreasesnoradrenergic transmission Adolescent binge drinking alters adult gene expressionresulting in decreased cholinergic neuron densitySpring, 2016Coleman (2011), Kim (2014), Sanchez-Mora (2013)59
Do lifestyle choices influence NT levels?Spring, 201660
Lifestyle factors can influence NT levelsNicotine blockscholinergicreceptorsSpring, 201661
Lifestyle factors can influence NT levels Exercise:ooAttenuated dopamine depletionIncreased serotonin and Ach levels Enriched environmentoUpregulates genes that balance NT activity Diet:oooSpring, 2016One-week of high-fat/low-carb diet decreased serotonin levels in thehypothalamusConsuming fat/sugar combinations reduced dopamine signalingLong-term consumption of low-protein/high-carb diet decreaseddopaminergic receptor densityKramer (2006), Lee (2013), Lopresti (2013)62
Valium? Inhibitory or Excitatory?Spring, 201663
Valium? Inhibitory or Excitatory?InhibitorySpring, 201664
GABA (inhibitory)ooNature’s “valium-like” substanceDrugs like valium, Ambien, Lunesta work by increasing theactivation of GABA-ergic receptor sitesBenzodiazepines (like valium) are effective in treating anxietySpring, 201665
How might GABA influence sleep? ADHD?Spring, 201666
GABA promotes sleepSpring, 201667
GABA levels decreased in ADHDSpring, 2016Edden, Crocetti, Zhu, Gilbert & Mostofsky (2012)68
Do we have any way to influence our GABAlevels?Spring, 201669
Increasing GABA Supplements not thoughtto cross BBB but may enterthrough enteric routes Animal data shows somebenefits in sleepSpring, 2016Boonstra et al., (2015); Mabunga, et al., (2015)70
What might happen if you increase GABA?Neurotransmitter MobileSpring, 201671
Why is Calvin mad?Spring, low-serotonin-may-be-the-culprit/72
Why is Calvin mad? He needs happy juice?Spring, low-serotonin-may-be-the-culprit/73
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Dopamine (excitatory & inhibitory) Involved in:oSpring, 2016Reward center/positive reinforcement75
Dopamine (excitatory & inhibitory) Involved in:ooSpring, 2016Reward center/positive reinforcementAbility to experience pleasure/pain76
Dopamine (excitatory & inhibitory) Involved in:oooooReward center/positive reinforcementAbility to experience pleasure/painMotivationEmotional response (altered levels seen in depression)Maintaining focus oSpring, 2016Stimulants/caffeine push dopamine into the synapse result is increasedfocus (long-term, causes dopamine depletion)Movement control77
Dopamine errors Motor/movement disorders ADHD (low levels) Addictions (mild elevations) Paranoia (high levels) Schizophrenia (very high levels)Spring, 201678
Do we want to increase dopamine levels?Neurotransmitter MobileSpring, 201679
Cocaine increases dopamine levelsSpring, imagebank/substance abuse/mao cocaine80
Cocaine causes short-term improvements butlong-term deficits in cognition (attention,flexible thinking) why?Spring, 201681
Long-term cocaine use induces plastic changes inthe reward circuit (nucleus accumbens)Spring, unction-of-the-nucleus-accum bens.html82
Can we legally influence our dopamine levels?Spring, 201683
Can we legally influence our dopamine levels?Spring, 201684
Exercise increases dopamine synthesisSpring, 201685
Serotonin (inhibitory) Helps regulate:oooSpring, 2016Mood (balances excitatory NTs to create stable mood)Hostility/aggression, arousalSleep (inhibits wakefulness)86
Serotonin (inhibitory) Helps regulate:ooooSpring, 2016Mood (balances excitatory NTs to create stable mood)Hostility/aggression, arousalSleep (inhibits wakefulness)Pain control87
Serotonin (inhibitory) Helps regulate:oooooooSpring, 2016Mood (balances excitatory NTs to create stable mood)Hostility/aggression, arousalSleep (inhibits wakefulness)Pain controlDigestionSensory perceptionHigher cognitive function88
What happens if we don’t have the rightserotonin level?Spring, 201689
Serotonin (inhibitory) Imbalance can cause:ooooSpring, 2016DepressionInsomniaDecreased immune functionCarbohydrate cravings90
Can we influence our serotonin levels?Spring, 201691
Medications alterNT levels byinterruptingneurotransmissionSpring, -action/92
Why are SSRIs preferred over valium foranxiety?Neurotransmitter MobileSpring, 201693
Valium is temporary; SSRIs induce plastic changes Benzodiazepines cause immediate GABA-like actions SSRIs cause plastic changes to change overall NT balanceSpring, 2016Gross (2004)94
Can supplements help? Tryptophan supplement(serotonin precursor)altered serotonin levels andbehavior in mice Vitamin D and omega-3smay modulate serotoninsynthesisSpring, 2016Patrick & Ames (2015); Zhang et al., (2015)95
Eat nuts, be happy?Spring, 201696
Animal data shows an increase in serotonin levelswith exerciseSpring, 2016Melancon (2014)97
Take a Quiz: Excitatory vs. InhibitorySpring, 201698
ExcitatoryoooooSpring, line)Epinephrine (adrenaline)Dopamine InhibitoryoooGABA (gammaaminobutyric acid)SerotoninDopamine99
Neurotransmitters—the big picture Neurotransmitters (NTs) communicate informationthroughout the brain & body NTs tell your heart to beat, lungs to breath, stomach to digest NTs regulate mood, sleep, hunger, concentration, andmore lack of balance can cause adverse symptoms Genetic and lifestyle factors influence NTbalance/levels/function NT levels are inter-related; you can’t alter one without alteringthe othersSpring, 2016100
Neurotransmitters influence each otherSpring, 2016101
Balance is key remember the mobileSpring, 2016102
Questions?juliav@maitrilearning.comComplete the ssion topics/90505Spring, 2016103
References Arnon, S. S., Schechter, R., Inglesby, T. V., Henderson, D. A., Bartlett, J. G., Ascher, M. S., .& Lillibridge, S. (2001). Botulinum toxin as a biological weapon: medical and public healthmanagement. JAMA, 285(8), 1059-1070. Boonstra, E., de Kleijn, R., Colzato, L. S., Alkemade, A., Forstmann, B. U., & Nieuwenhuis, S.(2015). Neurotransmitters as food supplements: the effects of GABA on brain andbehavior. Frontiers in Psychology, 6. Retrievedfrom 0/ Coleman (2011), Edden RE, Crocetti D, Zhu H, Gilbert DL, & Mostofsky SH. (2012).Reduced GABA Concentration in Attention-Deficit/Hyperactivity Disorder. Arch GenPsychiatry. 69(7), 750-753. Jedynak, J., Hearing, M., Ingebretson, A., Ebner, S. R., Kelly, M., Fischer, R. A., . & Thomas,M. J. (2016). Cocaine and amphetamine induce overlapping but distinct patterns ofAMPAR plasticity in nucleus accumbens medium spinyneurons. Neuropsychopharmacology, 41(2), 464-476. Mabunga, D. F. N., Gonzales, E. L. T., Kim, H. J., & Choung, S. Y. (2015). Treatment of GABAfrom Fermented Rice Germ Ameliorates Caffeine-Induced Sleep Disturbance inMice. Biomolecules & therapeutics, 23(3), 268. Marc, D.T., et al., (2010) Neurotransmitters excreted in the urine as biomarkers of nervoussystem activity: Validity and clinical applicability. Neurosci. Biobehav. Rev.doi:10.1016/j.neubiorev.2010.07.007Spring, 2016104
References, cont’d. Murphy, S. (2011). Neurobiology lecture notes. Harvard University (BIOE-50). Patrick, R. P., & Ames, B. N. (2015). Vitamin D and the omega-3 fatty acids control serotonin synthesisand action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. TheFASEB Journal, 29(6), 2207-2222. Qi Z, Tretter F, Voit EO (2014) A Heuristic Model of Alcohol Dependence. PLoS ONE 9(3): 0092221 Spronk, D. B., van Wel, J. H., Ramaekers, J. G., & Verkes, R. J. (2013). Characterizing the cognitiveeffects of cocaine: a comprehensive review.Neuroscience & Biobehavioral Reviews, 37(8), 1838-1859.Retrieved fromhttps://www.researchgate.net/profile/Laura Corbit/publication/260219047 Effects of Repeated Cocaine Exposure on Habit Learning and Reversal by NAcetylcysteine/links/00b495376cffb92c46000000.pdf Stahl, S. M. (2008). Selective histamine H 1 antagonism: novel hypnotic and pharmacologic actionschallenge classical notions of antihistamines. CNS spectrums, 13(12), 1027-1038. Sutoo, D. E., & Akiyama, K. (2003). Regulation of brain function by exercise.Neurobiology ofdisease, 13(1), 1-14. Zhang, W. Q., Smolik, C. M., Barba-Escobedo, P. A., Gamez, M., Sanchez, J. J., Javors, M. A., . & Gould,G. G. (2015). Acute dietary tryptophan manipulation differentially alters social behavior, brainserotonin and plasma corticosterone in three inbred mouse strains. Neuropharmacology, 90, 1-8.Spring, 2016105
Mind, Brain, Health, and Education Section: Neurotransmitters Harvard University Extension School (PSYCE-1609) February 2, 2016 1. Spring, 2016 2. Spring, 2016 3. Spring, 2016 Which of these is a neuron? 4. Spring, 2016 Which of these is a neuron? 5
