BISC 421 1st Edition Lecture 31 Outline of Current LectureI. Circadian Rhythms Part 2Current LectureCircadian Rhythm Part II•Circadian Rhythms-‐ outstanding mysteries •Central clock in the SCN-‐ cycle of Per protein expression is somehow translated into electrical output-‐ how is not yet known •Electrical output of SCN is translated into release of hormones (melatonin) that synchronizes the body and control sleep and wakefulness •SCN is not the only place in the body that has a “clock” in fact in most cells show circadian cycles of gene expression but they do not have an efect on the rest of your body •The clock in the SCN can be “entrained” by light but this entrainment only shifs the clock a little bit each day (about an hour a day for humans)-- each stage has a specific wave formSlow wave•Sleep monitor detectng the stages of sleep - Wave forms are refectve of aggregate activity-‐ if asynchronous then you then you see some fat actvity but if synchronized can see a lot of spikes.•A full cycle of going through sleep and coming back up is about 90 minutes•Each cycle has longer REM sleep•Dreaming during REM and muscle paralysis•Stage 4 the most important, although will not be asked if it is the most restoratveon test because REM might be•Clearly Stage 4 is not sufcient though•Don't really have an answer but it has been realized that there is some sort of restorative functon to sleep•Found to strengthen memory•Has been studied in the lab where volunteers do various tasks and then given sleep or not sleep and then tested again and found that performance was improved afer sleep•Subjects had to learn a fnger sequence tap (sort of like piano)•Improved performance afer sleep•Either waited 8-‐10 hours or slept 8-‐10 hours•20%!!•Classic experiment-‐ sleep is essental for life itself•Two rats on a platorm that rotated and both were measured EEG•When experimental rat fell asleep the platorm rotated so that he couldn't and then the other was allowed to sleep•Rats forced to stay awake decreased body weight and died•Has been tested in humans too-‐ humans have tried to stay awake and the longest that someone has stayed awake is 19 daysLesion is in ascending system in the brainstem- retcular actvatng system•Brain areas involved in sleep-‐ frst evidence of partcular brain area that is master control came from studies of sleeping sicknesses•Encephalitis-‐ makes people sleep a lot more because attacks sleep center of brain•Discovered upon autopsy that there was a partcular area called the brainstem reticular actvatng system that was attacked stimulate reticular activating system, animal is awakened stimulate thalamus, animal goes to sleep•Classic studies looked at which areas were necessary and sufcient for sleep•1. Retcular actvatng system-‐ if you stmulate with electrode you wake up animal•2. Thalamus-‐ makes you go to sleep if stmulated•There are several nuclei that are controlling sleep-‐ too complicated so just or two•Anthistamines: promotes arousal in TMN-‐ causes sleep because histamine causeswakefulness and its blocked•These projectons are sent THROUGHOUT the brain-‐synchronizes cortex so brain does the samething-‐ in dolphins only have the brain sleeps at a tme•Narcolepsy-‐Usually in response to a strong emotion•Sleep apnea-‐ obstructon of airways•Insomnia-‐ huge problem in the US and is caused by many factors•Scientsts were able to clone out the mutatons for narcolepsy and found it was a g protein receptor in a specifc part of the brain•Highly concentrated in these sleep wakefulness centers•Receptor for orexin (peptde neurotransmitter) that is release by the hypothalamus and its role was originally in food intake but also involved in wakefulness•Change food intake due to secondary efect of wakefulness.•For humans it is an autoimmune disease that causes a loss of orexin neurons not a genetic mutation-‐ may not have it from birthStudying sleep new ideas and methods•Synaptc scaling? During the day, synapses get potentated (through LTP) – but the needs to be corrected at some point as larger synapses use more energy andspace this system can become saturated•Once a post synaptc cell is fring as much as it can – at night you lower down all of thesynapses and bring them down a bit – consolidatng everything so that it fts•This hypothesis is testable by visualizing the synapses•During wakefulness, your synapses are getng bigger and strengthened and during sleep the opposite happensEvidence for synaptic scalingFound that in fies neuronal circuits synapse size or number increased afer a few hours of wakefulness but decreased if the fies were allowed to sleepStudying sleep-‐ New ideas and methods•Optogenetc control of sleep-‐ put gene for channel rhodopsin in orexin neurons (how?)•Stmulate with light•Introduce a gene for a channel into whatever neuron you want to make sensitve to light(any neuron in the brain)•Forms a channel that is opened by light-‐ ions come in to depolarize•Can stmulate any area you want with light to depolarize•Know orexin neurons are necessary for proper sleep wakefulness but is it a direct efect?•Found that it is a direct efect of orexin in wakefulness or