neurochemistry
synthesis of Ach
Acetyl CoA + choline via choline acetyltransferase (ChAT)
Elimination of Ach
via acetylcholinesterase to choline and acetate (choline is re-used)
synthesis of dopamine
tyrosine –> DOPA via tyrosine hydroxylase –> dopamine by decarbosylase
elimination of dopamine
via transport into presynaptic element and then into the surrounding glial cells. within the glia the DA is metabolized by MAO and COMT. MAO is initial step in degradation within CNS and COMT is initial step in periphery
synthesis of NE
part of catecholamine pathway; formed from conversion of DA by dopamine beta-hydroxylase
elimination of NE
MAO in CNS and COMT in periphery
syntehsis of EPI
from NE by PNMT
elimination of EPI
uptake into surrounding glial cells, metabolized by COMT
synthesis of serotonin
tryptophan –> 5-HTP by trytophan hydroxylase –> 5-HT by amino acid decarboxylase
elimination of serotonin
transport into pre-synaptic element and into glial cells by selective 5-HT transporters,metabolized by MAO to form 5-HIAA
types of receptors for Ach
nicotinic
muscarinic
muscarinic
role of nicotinic receptors
skeletal muscle
role of muscarinic receptors
cholinergic receptor in CNS
dopamine receptors and functions
D1-increased cAMP
D2 – decreased cAMP
D2 – decreased cAMP
describe alpha family NE/EPI receptors
alpha-1: increased IP3/DAG, post synaptic excitationn
alpha-2: decreased cAMP, presynaptic and postsynaptic inhibition
alpha-2: decreased cAMP, presynaptic and postsynaptic inhibition
describe beta family receptors for NE/EPI
beta-1 and beta-2: icreased cAMP, post synaptic excitation
major projection pathways of Ach
– neurons in basal nucleus provide Ach projction to entire cerebral cortex
– cholinergic neurons in septum project to hippocampus (part of limbic system)
– cholinergic interneurons of striatum and nucleus accumbens
– neurons originating in brainstem RF rpoject to thalamus (RAS)
– in spinal cord: motor neurons
– autonomic ganglia, parasymp
– cholinergic neurons in septum project to hippocampus (part of limbic system)
– cholinergic interneurons of striatum and nucleus accumbens
– neurons originating in brainstem RF rpoject to thalamus (RAS)
– in spinal cord: motor neurons
– autonomic ganglia, parasymp
where is GABA found
throughout CNS
cerebellum, hippocampus, cerebral cortex, spinal cord
basal ganglia
cerebellum, hippocampus, cerebral cortex, spinal cord
basal ganglia
where is glutamate found
throughout CNS, principle NT of projecting cells of cerebral cortex (coticostriate, corticospinal tracts)
where is glycine found
increased amount in spinal cord
substantia nigra
widespread throughout CNS
required co-ligand with glutamate for activation of NMDA receptor
substantia nigra
widespread throughout CNS
required co-ligand with glutamate for activation of NMDA receptor
what NT has the mesolimbic/mesocortical pathway
dopamine
describe mesolimbic/mesocortical pathway
dopaminergic neurons in the ventral trigeminal area of mesencepahlon project to limbic structures including the nucleus accumbens ad frontal cortical areas
describe nigrostriatal pathway and what NT uses this
neurons in substantia nigra compacta project to neostriatum – dopamine
describe tuberinfundibular pathway and what NT uses this
neurons in arcuate nucleus of hypothalamus project tot he pituitary, dopamine
describe where the medullar periventricular area is and what NT uses this area
region at base of 4th ventricle; BBB is here and permits neurons to go trhu, dopamine
NE is found in what areas of the medulla
locus ceruleus
subceruleus complex
dorsal medullary group
subceruleus complex
dorsal medullary group
what ascending projections is NE found in
projections of central tegmental tract, medial forebrain bundle,and DLF
what descending projections is NE found in
cerebellu, medullar and pontine RF, spinal cord
describe epinephrine distribution within CNS
limited distribution
descirbe where EPI is distributed in CNS
-medullary cell group
– ascending projections
– descending projections
– ascending projections
– descending projections
what ascending projections is EPI distributed in
locus ceruleus, PAg, thalamus, hypothalamus, CNX
what descending projections is EPI distributed in
intermediolateral cell columns of spinal cord
what two areas is serotonin found in
raphae nuclei (in pons and medulla)
ascending projection
ascending projection
where does the ascendign projection of serotonin distribution all go to
cerebral cortex, thalamus, thypothalamus, septal nuclei, basal ganglia
where is histamine distributd
reticular formaiton cell group
posterior hypothalamus
projections from hypothalamus that ascend to thalamus and cortex and descend to brainstem and spinal cord
posterior hypothalamus
projections from hypothalamus that ascend to thalamus and cortex and descend to brainstem and spinal cord
Ach behaviors associated with
– arousal (RAS)
– learning and memory (alzheimers)
– motor control (basal ganglia and muscle)
– autonomic function
– learning and memory (alzheimers)
– motor control (basal ganglia and muscle)
– autonomic function
dopamine is associated with what behaviors
– motor control – parkinsons = loss of DA
– thought processing: schizoprehnia = dysfuncion in DA
– endocrine control (D2) : – prolactin relase, + GH release
– nausea and vomiting
– thought processing: schizoprehnia = dysfuncion in DA
– endocrine control (D2) : – prolactin relase, + GH release
– nausea and vomiting
EPI is associated with what behaviors
– control of symp activity
– motor control of viscera
– food and water intake
– sensory modulation (pain)
– motor control of viscera
– food and water intake
– sensory modulation (pain)
serotonin is associated with what behaviors
– arousal
– hallucinations
– modulation of pain
– mood
– feeding
– temp
— CV reflexes and symp tone
– sexual behavrio
– nausea and vomiting
– CSF production
– cerebral bloodflow (vasoconstriction)
– hallucinations
– modulation of pain
– mood
– feeding
– temp
— CV reflexes and symp tone
– sexual behavrio
– nausea and vomiting
– CSF production
– cerebral bloodflow (vasoconstriction)
glutamate is associated with what behaviors
– fast exctitatory response in CNS
– memory learning (plasticity)
– neurotoxicity seen in cerebral ischemia
– pathogenesis of seizure disorders
– memory learning (plasticity)
– neurotoxicity seen in cerebral ischemia
– pathogenesis of seizure disorders
GABA is associated with what behaviors
– inhibitory neuronal fnction
– sedation
– anti-anxiety
– motor control
– pathogenesis of seizures
– sedation
– anti-anxiety
– motor control
– pathogenesis of seizures
glycine is associated with what behaviors
fast inhibitory effect
richest in inhibitory interneurons of spinal cord
facilitation of GLUT action at the NMDA receptor
richest in inhibitory interneurons of spinal cord
facilitation of GLUT action at the NMDA receptor
histamine is associated with what behaviors
– arouseal (RH pathway)
– food and water intake via posterior hypothalamus
– food and water intake via posterior hypothalamus
H1 receptor
post synaptic, excitatory
H2 recpetor
post synaptic, excitatory. incresaed cAMP – increased effect in hippocampus and cortex
H3 receptor
pre-synaptic, decreases cAMP, hypothalamus
glycine types of receptors
strychnine sensitive and insensitive
describe strychinine sensitive glycline receptor
post synaptic, fast IPSP
describe strychnine insensitive glycine receptor
NMDA related, enables activation of NMDA receptor by GLUT
describe NMDA receptor of glutamate
ligand-gated cation channel, post synaptic. slow EPSP, syanptic plasticity
describe AMPA receptor of gluatamte
post syaptic ligand gated ion channel fast EPSP
is kianate receptor of glutamate fast EPSP or slow EPSP
fast EPSP
describe metabotropic receptor of glutamate
increases IP3, pre and post synaptic, synaptic plasticity
describe GABA A receptor
ligand gated Cl channel, fast IPSP
describe GABA-B receptor
G protein coupled, decreases cAMP, decreases NT release