AACIMP 2011 Summer School. Neuroscience Stream. Lecture by Evgenia Belova.

1. Neurotransmittersystemsof the brain and their functions

2. Neurotransmitter, drugsandbrainfunction// Ed. ByR.Webster. Oxford University Press, London. 2001. J.R.Cooper, F.E. Bloom, R.H.Roth. ThebiochemicalbasisofNeuropharmacology. / Oxford University Press, USA; 2007. Е.И.Белова Основы нейрофармакологии Аспект Пресс. Москва. 2010.

3. Allbiologicalfunctionsaretheoutputofcomplexnetworkofinteractionsofneurons. Inspiteofthefactthatsimilarspikesaretheoutputofanyneuron, theresultoftheirteamworkisthecomplexofphysiologicalandpsychologicalconditionsandfunctions. 2.Differentneuronsinteractbysynapsecontacts. 3. Theinformationtransmitioninthechemicalsynapsesiscarriedoutbyneurotransmitters.

4. Schematicrepresentationofaexcitatorysynapseinthebrain

5. Schematic representation of a neuron Differentsynaptic arrangements of a neuron : axo-dendritic, B) axo-somatic, C) axo-axonic D) dendro-dendritic.

6. What is neurotransmitter? Neurotransmitter is a substance which is released at the end of a nerve fiber by the arrival of a nerve impulse and by diffusing across the synapseor junction effects the transfer of the impulse to another nerve fiber. (or muscle fiber or some receptor). Neuromodulatorsasopposedtoneurotrasmitters: don't have their own effect, they can only modulate the effect of neurotransmitters. Their actions are slow and can take hours. Their receptors are not always placed in synapses, but on different membranes inside and outside the neuron.

7. PostsynapticeventsIonicbasisforexcitatorypostsynapticpotentials (EPSPs) andinhibitorypostsynapticpotentials (IPSPs)

8. Theactionpotential: ionicconductancesunderlyingtheactionpotentialrecordedfromasquidaxon

9. Transmitterrelease

10. Ionotropicreceptor

11. Transmembranetopologyofthesubunitsofthreedifferentfamiliesofionchannelreceptorsdenotedas 4-TM, 3-TM and 2-TM receptors

12. Metabotropicreceptor

14. Gi – inhibits adenylyl cyclase

15. Gq – activates phospholipase-C

17. Themodel of a acetylcholine synapse ACh – acetylcholine ChAT - cholineacetyltransferase AchE - acetylcholine esterase CT - plasma membrane transporterofcholine VAT – vesicular amine transporter.

18. Nicotinicreceptorofacetilcholine

19. Schematicrepresentationofmuscarinicreceptor

20. Whatdoesacetylcholinedointhebrain? Acetylcholinehelps to regulate: movement cortical excitability arousal and sleep cognition and reward

21. Thedistributionofnoradrenerdicneuronsinthebrain

22. Brainareasreceivingaprominentnoradrenergicinnervation

23. Model of a noradrenaline synapse illustrating the presynaptic and postsynaptic events NE – noradrenaline; DA – dopamine; DOPA – 3,4-dihydroxyphenylalanine AC – adenylylcyclase; AR - adrenergic receptor; DAG - diacylglycerol; IP3 – inositoltriphosphate; PLC – phospholipase C; NET – plasma membrane noradrenaline transporter, VMAT – vesicular monoamine transporter.

24. Subdivisionsofalpha- andbeta-adrenoceptorfamilies Adrenoceptor alpha- beta- alpha-1 alpha-2beta-1 beta-2

25. Whatisthefunctionofnoradrenalineinthebrain? influence arousal selectiveattention emotionalbehaviour

26. Dopamine neuronal pathways AMYG, amygdala; CN, caudate nucleus; MFB, medial forebrain bundle; NcA, nucleus accumbers; OT, olfactory tubercle; PUT, putamen; SN, substantianigra.

27. Schematic model of a dopaminergic nerve terminal

28. Schematic diagram of the anatomical arrangement of D1and D2 receptors

29. Centralfunctionsofdopamine motoractivity psychoses rewardandreinforcement

30. Dopamineandmotorfunction

31. 5-HT neuronalpathways

32. Raphenucneiprojectionstothebrainregions

33. Thesynthesisof 5-HT

34. Model of a serotonin (5-HT) synapse AC – adenylylcyclase; DAG, - diacylglycerol; IPS – inositoltriphosphate; PLC - phospholipase C; SERT – plasma membrane serotonin transporter; VMAT – vesicular monoamine transporter

35. Essentialfeaturesof 5-HT receptorsubtypes 5-HT1A - thiractivationinduces hypothermia, increases food intakeand reduces anxiety 5-HT2A Well-known agonist at these receptors is LSD. All atypical neuroleptics such as clozapine, risperidone, olanzepine act as antagonists of these receptors. 5-HT3 receptors are ionotropic. Theyare best known for their stimulation of transmitter release (DA, NA, ACh, GABA). 5-HT4 –agonists of this receptors are being explored as possible cognitive enhancers. 5-HT5– Many usedinclinicantipsychotic agentsand some antidepressant drugs havehigh-affinity to this receptor where they act as antagonists.

36. Whatdoes 5-HT dointhebrain? 5-HT helps to regulate: mood anxiety sleep body temperature appetite sexual behavior movement intestinal motility cardiovascular function nociception

37. Differenttypesof GABA neuronsin CNS

38. Fastinhibitory GABA transmition

39. Chlorinedistributionandthe GABAAresponse

40. Schematic model of the GABAA receptor structure

41. Structureof GABAA receptor Subunitcombinationschangereceptorfunction

42. Metabotropic GABA receptors

43. Pathways for glutamate utilization and metabolism

44. Receptorsofglutamate Ionotropic –AMPA (predominantlyNa+/ K+ conductance) – Kainate (Na+/K+ /Ca2+conductance) –NMDA(predomimantlyCa2+, lessNa+conductance) – potential-dependent Playdistinctivefunctionalrole Canbetargetsfordifferentdrugs Metabotropic –mGluRgroupsI, II andIII Canbeimplicatedinmemory, pain, enxiety

45. Ionotropicreceptorsofglutamate

46. NMDA receptor

47. Functionalrolesofglutamatereceptors Epilepsy Pain Memory Excitotoxicity Development