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Fatal Familial Insomnia
genetic condition. Causes failure to enter deep sleep. Can lead to death
sleep related disorder that can occur during arousals from sleep
promotes awake state by increasing monoamine transmission (serotonin - raphe nuclei and NE - locus of coerulus to the thalamus)
promotes awake state by increasing monoamine transmission (serotonin - raphe nuclei and NE - locus of coerulus to the thalamus). Also Histamine and Orexin mechanism
promotes awake state via adenosine receptor antagonist
promotes sleep state by increasing GABA output from VLPO (hypothalamus) to inhibit cholinergic (pons-midbrain junction), histamine (TMN) and monoamines (raphe nuclei and locus of coerulus).
promotes sleep by blocking histamine transmission (TMN)
Kluver Bucy Syndrome
Bilateral medial temporal lesion (amygdala). decreased anxiety towards fear, hypersexuality, visual agnosia, hyperorality
Calcification of the anterior-medial temporal lobe. Loss of ability to percieve fear, recognize fear, or a deficit in experiencing fear.
Amnesia observed in chronic alcoholics. Vit B1 deficiency and degeneration in mammillary bodies and medial thalamus
progressive and exaagerated neurodegeneration of limbic system effecting the elderly. Beta amyloid plaques and tau tangles are present in histo stains. Specifically Entorhinal Cortex (medial temporal lobe) or basal forebrain and cerebral cortex
Hippocampal formation important for learning and memory formation; Associate Cortex <---> Entorhinal Cortex --perforant pathway--> Dentate Gyrus --mossy fiber--> CA3 --schaffer collateral--> CA1 ----> Subiculum ----> Entorhinal COrtex (back)
Morris Water Maze
Tests learning in Hippocampus. Hippocampal lesion results in rodent unable to find hidden platform even after numerous days of practice.
Prefrontal Cortex Lesions
Phineas Gage personality change after lesion here. Left lesion causes depression. Right lesion causes mania.
Basal Ganglia Loop Review (Know what is excitatory and inhibitory)
Voluntary Motor or Autonomic emotional feedback (Amygdala). Cortex ++++> Striatum ----> Pallidum ----> Thalamus ++++> Cortex (feedback)
Familial vs Sporadic Alzheimers Disease
Familial version is rare and due to an inherited mutation in PS1, PS2, or APP genes. Highly penetrant so for sure will get Alzheimers. Sporadic version is more common and due to a Single Nucleotide Mutation (point mutation) in ApoE (apoE4 mut causes Cys---> Arg 112). This is of low penetrance so at a higher risk for Alzheimers but not neccessarily doom to get the disease if you have apoE4 mutation.
Treatment for Alzheimers disease. Acetylcholinesterase inhibitor (increases levels of AcH at synaptic junction).
Treats Alzheimers via glutamatergic modulator on NMDA receptor. Remember AD is primarily a degeneration of glutamatergic synapses and LTP mechanisms.
Positive vs. Negative Schizophrenia
In general a malfunction of dopamine pathway. Positive symptoms (VTA-mesolimbic projections) are the presence of abnormal behavior, delusions, and hallucinationsc caused by hyperdopamine transmission to D2 receptors mostly. Treat with antipsychotic drugs (APD) which are D2 receptor antagonists. Negative symptoms (VTA-mesocortical projection) are absence of normal social behavior such as apathy, avolition, anhedonia, alogia, and inappropriate affect caused by low dopamine activity. These chronic symptoms do not respond to APD and are difficult to treat.
An extrapyramidal (nigrostriatal) side affect of APD treatment of schizophrenia. Resting tremor, rigidity, difficulty initiating movement. Treat with anticholinergic drugs.
An extrapyramidal (nigrostriatal) side affect of APD treatment of schizophrenia and L-DOPA treatment of Parkinson's disease. Characterized by uncontrollable movement of the face, mouth and tongue. No effective treatment for Tardive.
Atypical APD to treat Schizophrenia. Binds non-dopaminergic receptors (5HT2A, H1, A1). Works for positive and negative symptoms. Less side affects than typical APD
Chlorpromazine (phenothiazines) and Haloperidol (butyrophenones)
Typical APD to treat only postitive symptoms of Schizophrenia. Binds D2 dopamine receptors only. Has side affects like Tardive dyskinesia and parkinsonian syndrome.
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