PSY 3061 1st Edition Lecture 19Outline of Last Lecture I. Memory formation in hippocampusII. Long term potentiationIII. Long term results of LTPOutline of Current Lecture IV. Alcohol is an antagonistV. Memory blackoutsVI. Chronic alcoholism related amnesiaVII. DementiaCurrent LectureI. Alcohol is an antagonista. Alcohol is a GABA antagonistb. During alcohol intoxication, alcohol opens GABA receptorsand enables hyperpolarization of glutamatergic neurons by along Cl- influxc. LTP requires glutamate  alcohol reduces glutamate d. Depresses excitability of overall CNSe. During alcohol intoxication, alcohol blocks Ca2+ ions fromentering glutamatergic neurons, especially in the hippocampusf. Alcohol binds and stops NMDA channel from openingg. Also decreases LTPII. Memory blackoutsa. Overall, alcohol’s effect on GABA (+) and NMDA (-) inhibits LTP from occurringb. As a result events that occur during intoxication are nevertransferred into long-term memoryc. What’s worse, alcohol withdrawal may kill these brain cells in the long-run through a process called excitotoxicityd. Hyperexcitability of glutamate cells excitotoxicitye. Glutamate induced excitotoxicity form repeated alcohol withdrawli. First-time alcohol use  NMDA receptor (NMDAR) is blocked by ethanol, postsynaptic glutamatergic excitability is inhibited  will bind but only some where activate  postsynaptic cell thinks presynaptic cell is not getting enough activity (lessdepolarization) ii. Neuron puts more receptors on cell membrane because it wants original level of excitationiii. System releasing more glutamate and has more glutamate receptorsiv. Upregulation of glutamate can be dangerous v. Repeated alcohol use glutamatergic neurons are less sensitive to glutamate because there are so many NMDARsvi. Alcohol withdrawal: glutamatergic cells have too many NMDARs, when glutamate is released they become over-excitedvii. Repeated alcohol withdrawals: postsynaptic neuron dies from apoptosisviii. Glutamate activates the postsynaptic neuron too much, causing an unsafe amount of Ca2+ to enter cell. In very high levels of postsynaptic Ca2+, apoptotic genes will be expressed and cell will dieIII. Chronic alcoholism related amnesiaa. In addition to excitotoxity, long-term alcoholism is commonly associated with Wenike-korsakoff’s syndromeb. Actually separate disorders, where Wernicke’s usually precedes Korsakoff’s but they occur in the same person 80-90% of the timec. Wernicke’s encephalopathyi. Because of NMDA receptors up-regulation, glutamatergic brain networks are injuredii. Symptoms1. Vision problems, especially in eye movement 2. Ataxia~ dis coordinated muscle movement (e.g.reaching for coffee cup, over shooting or undershooting the reach)3. Confusion (e.g. not knowing how to leave the room)d. Loss of glutamatergic cells especially in the cerebellume. Korsakoff’s syndromei. Symptoms1. Severe amnesia2. personality changes3. physical problemsii. Progressive nature1. Early stages: antereograde episodic amnesia2. Later stages: severe retrograde amnesiaiii. Wernicke’s and Korsakoff’s occur not only in alcoholics, but also those with a severe thiamine (vitamin B1) deficiencyiv. Amnesia is probably a product of multiple tissue losses, especially in media diencephalonv. Progressive nature complicates its studyvi. Treating Wernicke’s-Korsakoff’s patients with thiamine does alleviate some symptoms, but often too much damage has been done for complete recoveryIV. Dementiaa. Cognitive impairments, mostly involving memory loss and impaired reasoning, sometimes personality changesb. Several diseases involve dementia as a symptomsc. Alzheimer’s disease constitutes 75%i. Neurodegenerative diseaseii. Most dementia onsets 65+ years of ageiii. Earliest symptoms occur before it is known to be AD1. Short term memory problems- difficulty remember recently learned information2. Worsened attention and planning, inflexibility3. Beginning of apathy, which tends to last duration of illness4. Depression symptomsiv. Intermediate symptoms of AD1. Decline in vocabulary (paraphasias) (e.g. a chair is a chair, a throne is a chair)2. Motor slowing and reduced coordination3. Failed recognition of well-known friends/family4. Wandering, irritability, labile affect, resistence to caregiversv. Advanced AD1. Language mostly gone2. Totally dependent on caregivers3. Interestingly, emotional signals are intactvi. Neurodegeneration begins before symptomsvii. Acetylcholinesterase inhibitors1. Frontline treatment for AD2. AChEls slow down the synaptic breakdown of acetylcholine3. Donepezil is most common and most researched4. Side effects bradycardia, nausea, anorexia, muscle spasms, nightmares, mania/depression,vision