Neurotransmitters PDF

neurotransmitters 1. mitochondria 2. vesicle w/ NT (like Ach) 3. receptor 4. synaptic cleft (where the biochem processes occur) 5. post synaptic receptors 6. voltage-gated Ca+ channels 7. fusion of vesicle w/ nerve terminal -> release NT 8. NT reuptake channel CHEMICAL SYNAPSE 1. A...

neurotransmitters 1. mitochondria 2. vesicle w/ NT (like Ach) 3. receptor 4. synaptic cleft (where the biochem processes occur) 5. post synaptic receptors 6. voltage-gated Ca+ channels 7. fusion of vesicle w/ nerve terminal -> release NT 8. NT reuptake channel CHEMICAL SYNAPSE 1. AP -> presynaptic terminal 2. depolarization of presynaptic terminal -> opens ion channels -> allow Ca2+ in 3. Ca2+ releases NT from vesicles 4. NT binds to receptor sites on the postsynaptic membrane 5. opening and closing of channels cause change in post-syn membrane potential 6. AP propagates through next cell 7. NT is inactived or transported back into presyn. terminal NT inactivation occur thru enzymatic catabolism or nerve cell or glial reuptake mainly in the synaptic cleft of a chemical synapse pre-syn. neurons convert: electrical signal -> chemical signal post-syn. behavior functions in an opposite direction NEUROTRANSMITTERS chemical substances synthesized in a neuron released during neuron excitation o depend on Ca influx synthesized in medulla of adrenal gland either excitatory or inhibitory responses actions occur in post-synp, post-synp or target cells (effectors) neurons communicate thru chemical synapse EXCITATORY INHIBITORY -glutamate -glycine & GABA -Na+ influx (hence the more +) -Cl- (hence more -) -depolarization -hyperpolarization photoreceptors are the only nerve cells that are active during hyperpolarization neurotransmitters BIOCHEMICAL CLASSIFICATION OF NTs ESTER AA AMINES PEPTIDES OTHER SUBS. Ach Inhibitory Catecholamines Opioids Purines -glycine -epi -endorphins -ATP -GABA -NE -enkephalin -ADP -dopamine - Excitatory endomorphins Soluble gases -glutamate Indoleamines -nociceptin -NO -aspartate -serotonin (5- -CO HT) Substance p Lipids Imidazole - amines endocannabinoi -histamine ds insert info from pg 5 CLASSIFICATION OF NT 1. functional classification -excitatory (depolarization) -inhibitory (hyperpolarization) *only place where its opposite is in photoreceptors depend on the receptor type 2. where the effects are -direct (ionotropic) -indirect (metabotropic) NTs ARE ACTIVATED IN 3 WAYS 1. degradation by enzymes from the post-syn cell or within the synaptic cleft 2. reuptake by glial (astrocytes) or the pre-synp cell 3. diffusion away from the synapse thru the bloodstream ACH 1. skeletal muscle: contraction 2. heart muscle: inhibition of contraction other functions Cortical excitability Heart and Skeletal Muscle Contraction Arousal and sleep Cognition and reward ¨ >ACh is made from choline + acetyl CoA neurotransmitters o Acetyl-CoA comes from glycolysis (converted by enzyme pyruvate dehydrogenase) o choline acetyltransferase (ChAT) is the rate limiting step in the pathway o Ach is then packaged into vesicles by a vesticular acetylcholine transporter (vAChT) o ¨ >Ach is broken down by enzyme acetylcholinesterase ¨ >choline -> back to axon -> make more Ach Choline Na+ transporter 1) choline: in 2) Na+: out ACH secretion location CNS PNS ¨ cerebral cortex ¨ NMJ of muscles ¨ hippocampus ¨ all pregang, parasymp & ¨ brainstem postgang fibers of ANS SYMPATHETIC PARASYMPATHETIC Pregang: Ach Pre & post gang: cholinergic Postgang: CHOLINERGIC-ACETYLCHOLINE RECEPTORS NICOTNIC MUSCARINIC ¨ N1 (Nm): @ NMJ of skeletal ¨ M1 – M5 muscles (M4 & M5 are rare) ¨ N2 (Nn): in pre/post neurons of parasymp NS & ¨ M3: pupil constriction & post neuron of symp NS activation of lacrimal -autonomic ganglia, CNS, gland secretion adrenal medulla) ACH associated effects ¨ exposure to insecticides -> prolonged effects of Ach -> leads to tetanic muscle spasms ¨ inhibited by botulinum toxin o produced by clostridium botulinum o same toxin that causes food poisoning ¨ Alzheimer’s : decreased ACh levels ¨ Myasthenia Gravis: nicotinc Ach receptors destroyed neurotransmitters ¨ atropine o mydriatic drug: dilated pupil o anti-muscarinic cholinergic drug § tx: bradycardia, uveitis, early amblyopia in children o paralyses accommodation reflec: cycloplegic CLINICAL CORRELATIONS Alzheimer’s disease ¨ cholinergic neurons of basal forebrain affected o involved in learning & memory ¨ characterized by extensive neural atrophy in the brain cortex, hippocampal formation, dramatic loss of cholinergic neurons in Meynert ¨ symptoms o memory loss o personality changes o dementia ¨ tx o replacement therapy § donepezil § galantamine Huntington’s disease/ Huntington’s chorea ¨ result of degeneration of ACh & GABA ¨ pt has chorea (sudden, unexpected & purposeless contraction of proximal muscles) & dementia ¨ muscle rigidity, slow or unsual eye movements, problems walking or maintaining posture, speech & swalling deficits ¨ atrophy of brain basal ganglia & lateral ventricle enlargement ¨ decreased ACh release ¨ weakness on limb muscles (weak contractions) ¨ 50% associated with neoplasms (lung, breast, prostate) ¨ associated w. ANS dysfunction (invol, most dry mouth) DOPAMINE “pleasure chemical” ¨ coordination & mvnt ¨ attention, memory & learning ¨ arousal & sleep ¨ behavior & cognition ¨ inhibition of prolactin production ¨ nausea & vomiting ¨ inflammation & pain imbalances lead to ¨ sleep disturbances ¨ restless legs syndrome ¨ psychosis ¨ apathy/depression ¨ ADHD symptoms ¨ the longer you use a drug -> more more you’ll need to get a response o hedonic: max stage a person can reach -> addictive behavior o alcoholics have an increased state: need more to reach threshold inactivated by ¨ monoamine oxidase & catechol-o-methyltransferase o @ liver, presynp or postsyn terminal secreted at ¨ CNS o substansia nigra (pars compacta) § GABA-associated nuclei: inhibitory o VTA of midbrain o hypothalamus (arcuate nucleus) neurotransmitters § control energy metabolism in peripheral tissues § regulate hunger & thirst § inhibit prolactin? ¨ PNS o some sympathetic ganglia Dopamine receptors ¨ D1: working memory (short term: related to thinking & speaking) ¨ D3: addiction behaviors ¨ D4: wide functions in amygdala, hippocampus, pit gland & RETINA supplements that affect dopamine levels AGONIST ANTAGONISTS ¨ yohimbine (ED, lose wt, ¨ L-theatine agina) ¨ ginkgo biloba ¨ nindong granules ¨ bacopa ¨ mucuna pruriens high DA levels: tics, involvuntary mvnts, euphoria, hallucinations & psychosis low DA levels: Parkinson’s disease DA effects ¨ “feel good” MT ¨ l-dopa in tx parkinson’s disease ¨ amphetamines enhance DA levels ¨ schizophrenics: increased production ¨ nucleus accumbens receive inputs from the VTA -> reinforce learning & evading aversing stimuli neurotransmitters CLINICAL CORRELATIONS Parkinson’s disease ¨ degeneration of dopaminergic neurons in the substantia nigra (reduce release of DA in caudate/putamen in basal ganglia) ¨ tremors, rigidity, akinesia (loss of ability to voluntarily more muscles) ¨ Tx o L-dopa o carbidopa Schizophrenia ¨ most common psychotic disorder ¨ increase activity at dopaminergic synapses ¨ Tx o phenothiazines o butyrophenones (reduce DA synaptic activity in limbic forebrain) Cocaine drug abuse ¨ local anesthesic drug that inhibit the reuptake of DA & NE into the nerve terminals ¨ responsible for euphoric effects ¨ DA projections from the VA to the NAcc: emotional reinforcement & motivation associated with cocaine addiction neurotransmitters DA increasing drugs ¨ heroine cocaine (crack & powder) ¨ crystal meth ¨ ecstasy (MDMA derivative) ¨ pure MDMA ¨ bath salts ¨ marijuana ¨ LSD ¨ alcohol ¨ rx painkilles ¨ benzodiazepines ¨ caffeine ¨ pts experience withdrawals when they stop taking these after prolonged use o bc the brain is used to getting them so when it doesn’t have it feels sick & pain NOREPINEPHRINE ¨ indirect action via 2nd messengers o metabotropic NT o location § CNS: locus coeruleus nuclei A6 limbic system some areas of cerebral cortex § PNS main NT of postgan neuron in the symp nervous sym FEF is responsible for saccadic eye movements for the purpose of visual field perception & awareness as well as for voluntary eye movement. neurotransmitters ¨ play a role in the genesis & maintenance of mood ¨ amphetamines enhance the release ¨ catecholamine hypothesis: reduced NE activity is related to depression ¨ increase NE related to mania EPINEPRHINE ¨ can be synthesized in neurons in the adrenal medulla o transported back to neurons or used in tissues ¨ C1 neurons: rostral ventrolateral medulla ¨ C2 neurons: nucleus tractus solitarius or solitary nucleus SEROTONIN; 5-HYDROXYTRYPTAMINE; 5-HT ¨ an indoleamine ¨ dietary tryotophan serves as a substrace for serotonin synthesis ¨ functions o mainly inhibitory o indirect action via 2nd messengers o direct action at 5-HT receptors ¨ location o CNS § brainstem (dorsal & medial raphe nuclei) midbrain medulla pons neurotransmitters § send projections to hypothalamus limbic system (learning & memory) cerebellum pineal gland (melanin secretion) spinal cord (nociception) serotonin receptors INHIBITORY STIMULATORY 1, 5, 6 2, 3, 4 serotonin effects ¨ play a role in sleep, appetite, nausea, migraine, regulation of mood, body temp & pain Low 5 HT levels High 5 HT levels Depression & insomnia Mania Prozac (blocks reuptake of OCD serotonin) (tricylic antidepressant) ¨ selective serotonin receptor agonist for 5-HT can abort migraines (due to vasoconstrictive & anti-inflammatory effect) GLUTAMATE ¨ derived from AA ¨ function o excitatory NT ¨ sources o krebs cycle o reuptake of glu ¨ alzheimer’s disease o loss of neurons by overexcitation & glutamate-induce activation of NMDA § Tx: Namenda; receptor antagonist ¨ Glutamate in retina o on: hyperpolarization -> mGluR6 -> activates photorecp o off: AMPA/kainite receptors neurotransmitters