Neurochemical Organization of the Brain Flashcards
What are the two roles of Norepinephrine (NE) in the brain?
Where is NE released in the brain?
Arousal/alterness & regulation of memory formation via emotion
The Locus Coeruleus (all other NE neurons branch from here)
What are the 2 preursors to Norepinephrine and what are the enzymes that convert them?
What enzyme breaks down NE and where is it located in the neuron?
L-Tyrosine -Tyrosine hydroxylase (TH)-> L-Dopa
L-Dopa -L-Amino acid Decarboxylase (AADC)-> Dopamine
Dopamine -Dopamine beta hydroxylase (DBH)-> NE
NE is broken down by Monoamine Oxidase A found in mitochondria, and then it is converted to 3-methoxy-4-hydroxy-phenylglycol (MHPG) outside the cell by Catechol O-Methyltransferase (COMT)
How is stress signalled throughout the BODY?
Hypothalamus perceives stress
Sends Corticotropin-releasing Hormone
Pituitary secretes Adrenocorticotropic hormone
Adrenals secrete glucocorticoids (including cortisol) to the brain
GCs act negatively on Hippocampus and Hypothalamus
What are the two types of receptor for cortisol and how do they differ?
Mineralocorticoid receptors (type I high affinity) activated by basal levels of cortisol Glucocorticoid receptors (type II low affinity) activated by stress levels of cortisol
What are two functions of Dopamine (DA) in the brain and how do we know it is implicated in psychotic disorders?
Where is DA released in the brain?
Motor Control & Motivational Control
Antipsychotic drugs block DRD2 receptors (discovered serendipitously
Released in the Mesolimbocortical pathway or Mesostriatal pathway
What is the only step in Dopamine synthesis that differs from Norepinephrine synthesis?
What are the breakdown products of DA and where do these reactions take place?
DA synthesis stops before DBH step
DA -MAOB-> Dihydroxyphenyl-acetic acid (DOPAC)
DOPAC -COMT-> Homovanillic acid (HVA)
What are 4 of the 12 functions of Serotonin/5-hydroxytryptamine (5-HT)?
Where is 5-HT produced? What are this area’s sublocations and which axons are found where?
CV/respiratory activity, sleep, aggression, sexual behaviour, nutrient intake, anxiety, mood, motor output, neuroendocrine secretion, nociception and analgesia
Raphe Nuclei - divided into two sections
Rostral and Caudal Raphe Nuclei
Rostral divided into Dorsal Raphe and Median Raphe
Dorsal raphe axons are fine and rarely make synapses
Median raphe axons are coarse and show synaptic specialisations
How is 5-HT synthesized?
How is 5-HT degraded?
L-Tryptophan -Tryptophan Hydroxylase (TrH)-> 5-HTP
5-HTP -AADC-> 5-HT
5-HT -MAOA-> 5-HIAA
How does chronic SSRI (antidepressant) lead to depression?
Chronic use decreases 5-HT uptake, perhaps by inducing internalization and degradation of SERT
How does MDMA cause non-vesicular release of 5-HT?
Inhibits VMAT causing increased intracellular 5-HT, causing it to backflow out of SERT
What are the 3 types (and various subtypes) of 5-HT receptor?
5-HT1:
1A: autoreceptors to inhibit serotonin release from terminals
1B/D: presynaptic receptors on basal ganglia
5-HT2: Postsynaptic receptors that decrease K+ conductance/increase excitability of neurons
5-HT2A cerebral cortex/basal ganglia
5-HT3: ligand gated ion channels permeable to Ca2+
Describe the concepts of spatial and temporal summation
Temporal summation: One sensory neuron firing rapidly in succession causes an increase in motor neuron stimulation
Spatial summation: Two sensory neurons firing simultaneously causes an increase in motor neuron stimulation
What is the primary neuroexcitatory amino acid?
What are its ionotropic receptor types? What are its metabtropic types?
Glutamate
Ionotropic - NMDAR, AMPAR, KAR
Metabotropic - Class I, II, or III
How are NMDARs implicated in Schizophrenia and Depression?
NMDA receptor antagonists induce psychosis and impair working memory
Long term TCA antidepressant use reduces the expression of NMDAR receptors
