Sleep
The secretion of what hormone is suppressed by blue light?
Melatonin
What molecule is the precursor to GABA?
Glutamate
What is given in paracetamol overdose?
N-acetylcysteine
What amino acid is dopamine derived from
Tyrosine
Which major class of drugs is used in the Tx of depression?
SSRIs
Which hypothalamic nucleus serves as the mammalian "master clock," coordinating systemic daily rhythms to the external day-night cycle?
Suprachiasmatic Nucleus (SCN)
Explain the difference between GABA-A and GABA-B receptors?
GABA-A = Ionotropic: ligand gated ion channel, binding of GABA cause Cl- influx
GABA-B = Metabotropic – G protein coupled receptor – 2nd messenger that results in K+ efflux
What are some pathologies associated with the GABA-A receptor?
Anxiety disorders, epilepsy, alcoholism
Where is serotonin primarily synthesised?
Raphe nucleus
What are the clinical features of depression?
Depressed mood, Anhedonia, Feelings of guilt or thoughts of worthlessness, Sleep disturbance e.g. hypersomnia or insomnia, Fatigue, concentration difficulties, appetite, psychomotor, suicidal ideation
What EEG rhythms are characteristic of stage 1 NREM sleep?
Theta rhythms
What term describes the effect that alcohol and BZDs have on GABA receptors?
allosteric modulator
Progressive degeneration of dopaminergic neurons located in this nucleus results in the motor symptoms of Parkinson's Disease
Substantia Nigra
Which neurotransmitter has predominantly inhibitory action linked to movement, reward, memory, lactation, attention, sleep regulation, nausea, motivation, arousal?
Dopamine
Under chronic stress, hyperactivation of the HPA axis causes a sustained release of this hormone
Cortisol
Sustained cortisol elevation inhibits neurogenesis and BDNF expression, causing hippocampal atrophy, which is consistently observed in neuroimaging of clinically depressed individuals
Which 2 systems antagonise each other and act as a "flip flop" circuit to induce sleep or drive wakefulness?
VLPO (ventrolateral preoptic nucleus) - induce sleep
ARAS (ascending reticular activating system) - drives wakefulness
MOA of temazepam?
BZD binds a subunit
Potentiates the effects of GABA (increases frequency of channel opening) --> allosteric modulation
Activation of GABA-A receptor results in increased permeability and influx of Cl- --> hyperpolarisation (neuronal inhibition)
Anxiolytic effect due to rapid suppression of excitatory neurotransmission throughout the brain
Damage to the nucleus basalis (of Meynert) often manifests as what disorder?
Alzheimer's disease
Loss of cholinergic neurons (and therefore ACh) in the nucleus basalis of Meynert occurs in Alzheimer's Diseases (and short term memory loss).
Acetylcholinesterase inhibitors are used for treatment, but are only modestly effective.
What is the primary noradrenergic nucleus?
Locus Coeruleus
What is the timeframe for clinically diagnosing depression vs generalised anxiety?
Depression - at least 2 continuous weeks
Anxiety - at least 6 months where excessive worry occurs more days than not
Explain the effect of light on circadian rhythm?
Light stimulates intrinsically photosensitive retinal ganglion cells (IPRGC/MCRGC) --> stimulates SCN via retinohypothalamic tract (RHT) --> inhibits melatonin secretion by pineal gland and indirectly inhibits VLPO
Explain the pathophysiology of excitotoxicity.
Failure of glucose supply (no ATP)--> decrease GLU uptake by astrocytes --> increase GLU in synapse --> hyperactivation of NMDA receptors --> influx of Ca+ post synaptically --> cascade that results in apoptosis
Which pathways are proposed to be implicated in schizophrenia?
The VTA pathways (mesolimbic + mesocortical)
Dopamine pathway therefore dysregulation causing increased DA --> abnormal salience or valence attached to stimuli
Where do cholinergic neurons in the reticular system project to?
Cortex, thalamus, limbic system
The monoamine theory of depression posits that depression is caused by a functional deficit of which neurotransmitters?
Noradrenaline, 5-HT and dopamine