6_Transmission - Different axons according to their...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Different axons according to their function Thoughts, feelings, behavior, … Motor Somatosensory Autonomous are all the consequences of electrical and chemical brain activity thick thin A materialistic vision Action potential sodium (Na+) potassium (K +) 1 Action potential The central neurotransmitters are not exclusively located in the CNS Example: dopamine-synapse Dopamine receptor DOPA Dopamine Dopamine transporter => unwanted (“adverse”) effects of CNS drugs Presynaptic Synapic cleft Postsynaptic 2 Acetylcholine Some neurotransmitters •Muscarinic receptors: primary Ach receptor in CNS Biogenic amines • Acetylcholine • Catecholamines – Dopamine – Noradrenaline (Norepinephrine) – Adrenaline (Epinephrine) • • • GABA Glutamate Aspartate • Indolamines – Serotonin – Histamine 1 Nu. tractus diagonalis => hippocampus (role in memory) Amino acids 2 Nu. basalis (Meynert) => neocortex 1 2 Opioids •Nicotinic receptors: also implicated in PNS Dopamine Synthesis of catecholamines -dopamine -noradrenaline -adrenaline Dopamine is formed from tyrosine. Dopamine degradates to DOPAC and the nocious products: oxygenperoxide en hydroxyl radicals. Tyrosine Tyrosine hydroxylase Dihydroxyfenylalanine DOPA decarboxylase Dopamine Monoamino-oxidase (MAO) DOPAC Oxygenperoxide, hydroxyl radicals Waterstofperoxide & hydroxyl-radicalen 3 Dopamine systems Four central dopaminergic systems: Dopamine systems extrapyramidal system executive and memory reward mediated behavior •Nigro-striatal •Meso-limbic •Meso-cortical •Tubero-infundibular -Nigro-striatal path: dopaminergic neurons in substantia nigra project to the striatum Dopamine systems -Mesocortical path to frontal cortex (DLPFC) -Mesolimbic path to the limbic system Dopamine systems Putamen Caudate nucleus Nucleus accumbens Ventral tegmental area Amygdala Substantia nigra mesolimbic pathway Dopamine mediates reward mediated behavior D3 receptor nigrostriatal pathway D2 receptor Missale C, et al. Physiol Rev 1998;78:189-225 Shafer RA, et al. Psychopharmacology (Berl) 1998;135:1-16 4 Noradrenaline Noradrenaline projections to cortex, cerebellum and spinal cord Locus coeruleus: a noradrenergic nucleus in the pons, at the bottom of the 4th vertricle Serotonin Noradrenergic functions Tryptofaan • Dorsal bundle and median forebrain bundle – arousal, sleep-wake system – autonomic functions – reward and reinforcement – affect (anxiety, mood) Tryptofaanhydroxylase 5-hydroxytryptofaan 5-hydroxy-tryptophan Aromatic L-amino acid decarboxylase Serotonine (5-HT) (5-hyroxy-tryptamine) Monoamino-oxidase (MAO) • Implicated in drug addictions and withdrawal syndromes 5-HIAA Formed from tryptophane. The enzyme monoamino-oxidase (MAO) degradates serotonin. One of these products is 5-HIAA. 5 Serotonin Serotonin projections Involved in appetite, sleep, memory, impulsivity mood, ... Raphe nuclei in the brainstem Projections (red arrows) from the rostal (dorsal) raphe nucleus (RRN) and from the caudal raphe nucleus (CRN) There are also projections from the median raphe nucleus and from the RRN, for example to the hippocampus (not shown). C, cerebellum; Th, thalamus; A, amygdala; TL, temporal lobe; ST, striatum; PFC, prefrontal cortex; OC, occipital cortex. Some serotonin receptor types Serotonin receptors: 7 types, 14 subtypes! • 5HT1a – high concentration in hippocampus, amygdala, septal area – agonists are anxiolytic and antidepressant – some suggestion of antiaggression (low conc. of 5HT1a receptors in frontal cortex of violent suicide victims) • 5HT2 – high concentration in the neocortex and in parts of the subcortex – role in thermoregulation, appetite and vegetative functions – in subcortex, involved in gating sensory information (LSD) Dopamine, noradrenaline and serotonin: intense interrelationship in the regulation of ‘mood’ 6 Biogenic amines • Acetylcholine • Catecholamines – – – • Dopamine Norepinephrine (noradrenaline) Epinephrine (adrenaline) Some amino acids as neurotransmitter Indolamines – – Serotonin Histamine • • • • GABA Glutamate Aspartate … Intense interrelationship between various biogenic amines in the regulation of wake and sleep GABA Amino acids • GABA • Glutamate • Aspartate Gamma-amino-buturic acid • Primary inhibitory neurotransmitter in CNS Derived from glutamate: marker enzyme is Glutamic Acid Decarboxylase • Strong relationship with dopamine in nigrostriatal system and mesolimbic system – GABA inhibits dopamine neurons – role in movement, affect, memory, anxiety, sleep Amino acids • GABA • Glutamate • Aspartate Glutamate, Aspartate • Glutamate and aspartate are major excitatory neurotransmitters • Major role in LTP (memory, learning) • Glutamate: widely available food additive (allowed): E 621, monosodium-glutamate, ve-tsin, the 5th taste (in chips, chinese food …): difficult to stop eating (glutamate stimulates the brain) 7 Opioids Receptor location: brain and spinal cord • Periaqueductal grey matter (analgesia) • Amygdala (retrograde amnesia) •… Endogenous ligands 1. Enkephalins: methionine, leucine 2. Endorphins 3. Dynorphins Involved in learning and memory, stress, pain Example of interaction of different neurotransmitters Working mechanisms of some drugs The importance of knowing the working mechanism of drugs e.g. neuroleptics 8 The blood brain barrier Lipophilic drugs easily pass the BBB Hydrophilic drugs hardly enter the brain. FUNCTION ----- 9 ...
View Full Document

Ask a homework question - tutors are online