Neurotransmitters Flashcards
Method of termination for glutamate
Re-uptake
Methods of glutamate synthesis in brain
Glucose via TCA cycle
Glutamine
Types of Glutamate Receptors
NMDA
AMPA
Kainate
(All ionotropic)
Permeability of NMDA receptors
Sodium, like all receptors, but especially the second messenger calcium
NMDA Receptor Activation Mechanism
Voltage and ion gated.
Depolarization is necessary to remove the magnesium ion that clogs the pore, and then an agonist (glutamate) and co-agonist(glycine or d-serine) must bind for activation
Key effects of Calcium entry through NMDA channels
Synaptic plasticity: Long-term potentiation which is thought to underlie memory formation
Excitotoxicity: Excessive calcium entry leads to cell death in some cases
Clinically useful glutamatergic drugs
Ketamine: Binds to the Magnesium binding site and inhibits NDMA activation
GABA Localization
Interneurons throughout the brain
Types of GABA receptors
GABAa- Allows Cl- entry, leading to hyperpolarization
GABAb- causes K+ to leave (efflux), also leading to hyperpolarization
Glycine Localization
Brainstem and spinal cord
In the forebrain, it serves as an important co-agonist for NMDA receptors
Catecholamine Biosynthesis Pathway
Tyrosine converted to DOPA via tyrosine hydroxylase
DOPA converted to Dopamine by DOPA decarboxylase
Dopamine converted to norepinephrine via Dopamine B-hydroxylase
3 Important Dopamine Systems in the Brain
Nigrostriatal
Mesocortical/mesolimbic
Tuberoinfundibular
Nigrostriatal System (Cell origin/function)
Cells origin in the substantia nigra and project to the striatum
Key role in movement initiation
Mesocortical/Mesolimbic System
Cells originate in ventral tegmental area and prject to prefrontal cortex/ventral striatum
Part of “reward pathway”, so important role in regulation of mood and drug abuse
Tuberoinfundibular System (Cell origin and function)
Cells originate in hypothalamus and project to the pituitary
Controls prolactin secretion (regulates lactation)
Norepinephrine Localization in the brain
Noradrenergic neurons are in the locus coeruleus, and account for the majority of adrenergic input to the limbic system
Function of Noradrenergic Pathways
Attention, arousal, vigilance, mood regulation
Serotonin Biosynthesis Pathway
Tryptophan to 5-HTP via tryptophan hydroxylase (rate-limiting enzyme)
5-HTP to serotonin via Aromatic L-amino acid decarboxylase
Serotonin Inactivation Mechanism
Re-uptake
Serotonin Pathways in the Brain
Median raphe nucleus contains serotonin cell bodies that innervate the parts of the limbic system, which is in the forebrain
Histamine Localization in the Brain
Tuberomammillary nucleus, located in the posterior hypothalamus
Mechanism of inactivation for histamine
Re-uptake
Function of histamine in the brain
Arousal (hence, antihistamines are used to treat insomnia)
Acetylcholine Biosynthesis
Choline and Acetyl-Coa are combined by choline acetyltransferase
Choline uptake is the rate-limiting step