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Introductory Neurobiology Week 8 Day 2 Notes

by: lucy allen

Introductory Neurobiology Week 8 Day 2 Notes Biol 3640

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Notes for Thursday, 2/25/2016, day two of week 8.
Introductory Neurobiology
Dr. John C Kinnamon
Class Notes
introductory neurobiology, neurobiology, Biology
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This 11 page Class Notes was uploaded by lucy allen on Thursday March 10, 2016. The Class Notes belongs to Biol 3640 at University of Denver taught by Dr. John C Kinnamon in Fall 2016. Since its upload, it has received 15 views. For similar materials see Introductory Neurobiology in Biology at University of Denver.


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Date Created: 03/10/16
-oral cavity provides a pathway for taste AND smell -chewing on jelly beans with nasal cavity blocked, no smell Chemosensory Systems in Mammalian Nose -olfaction goes directly to the primary olfactory cortex, does not stop at the thalamus like all other senses first -main olfactory -general odorants -accessory olfactory (vomeronasal) -pheromones -trigeminal (chemisthesis) -irritating/pungent volatiles -the olfactory system and instinctive behaviors -Pheromones are used in intraspecific behavior (behavior within a species) -Predators are detected by animals, causing behavioral responses usually promoted to escape and survival -Animals have stereotyped fear responses in response to odor -sexual -maternal -aggression Olfaction (Smell) -our sense of smell -can really influence and alter our mood -can influence how long we stay in a room -sharpens our awareness of other people, places and things -can influence who we talk to and who we want to talk to again -Important for quality of life -Cologne: a tiny sense of Johnson’s baby powder, makes the man feel good about himself when wearing it -Major histocompatibility complex -people are attracted to other people who's MHCs are significantly different (“good chemistry”) -people with similar MHCs do not have good chemistry -early warning system -fires -sour milk -burning food -"the Dogtor is in" -Dogs sense of smell is over 100,000 times more acute than humans’ -Uncanny ability to identify diseases in people (cancers, etc.) -from urine, breath, smell from body odors, etc. -99% accurate versus biopsies -can detect when people are going into a diabetic episode -breast cancer, lung cancer, moles/melanoma -flavor -bitter -sweet -sour -salty -umami -Involves both taste (20% of flavor) and smell (80% of flavor) -retronasal -back through pharynx, up to the nose -Olfaction and the Limbic System -Regions in our brain that are associated with memory and emotion -amygdala: fear, emotional response -odors have emotional context -hippocampus: memory -olfactory cortex is close to the entorhinal cortex, which is close to where the brain stores its memories -don’t have gustatory memory attachment because the gustatory brain structures are not close to the area of memory storage -odor and memories -recall -vision: 50% accurate after only three months -smell: 65% accurate after a year -structure of the nose -Odors come in through inhaled air or retronasal pathways -The olfactory epithelium is located in the route of the nasal cavity and the olfactory receptor cells have axons, which are the olfactory nerves, which pass through the cribriform plate, thin bone. -Then in the brain the first synapse in the olfactory pathway takes place in the olfactory bulb -Olfactory receptor cells are true neurons, and since their first synapse is in the olfactory bulb of the brain the olfactory receptor neurons are considered to be part of the central nervous system -the olfactory epithelium -the nose is the gateway to the brain -potential risks of trauma to the nose -Since they have a direct pathway, they provide a pathway for bad things -brain amoeba from hot springs -enters through the cilia and travels through the olfactory receptor neuron through the axons and into the olfactory bulb -the site of transduction in the olfactory receptor neuron are specialized cilia that emanate from the apical region of the olfactory epithelium -true cilia, 9 doublets of microtubules -situated upside down inside the route of the nasal cavity -through the cribriform plate and then part of the brain in the olfactory bulb -in a human the olfactory bulb is very small, smaller than pinky fingernail -in mice and dogs relatively speaking are very large -Glomeruli: spherical shape aggregations inside the olfactory bulb -Labeled line system going into the glomeruli -approximately 10,000 odors a human can discriminate between -some people can detect up to 100,000 different odorants -we have approximately 300 olfactory receptors -mice have about 1,000 -each receptor basically has a glomerulus of its own -all of the olfactory receptor neurons expressing receptor X go to a glomerulus specifically for olfactory receptor neurons expressing receptor X -the olfactory pathway -Olfactory epithelium, to olfactory bulb, from olfactory bulb to Olfactory Cortex, then to the thalamus, other destinations along the way -transduction mechanisms in mammalian nose -Odorant binds a GPCR, G protein alpha subunit breaks away and stimulates adenylate cyclase, converting ATP to cAMP, opening a cation channel for passage of sodium and calcium -Calcium then opens up a calcium activated chloride channel, and chloride leaves the olfactory receptor neuron, further depolarizing the cell (IN THE CILIA) -the olfactory receptor neuron -Like a typical neuron, when an olfactory receptor neuron is stimulated, a potential is stimulated -Once reaching the cell body it becomes an action potential, travels down the olfactory nerve until it reaches a glomerulus, where it synapses onto another cell -common odors -vary from simple structure (ethanol, dimethyl sulfide) to very complex structure (androstenone: essence of male pig) -female pigs in estrus smell the androstenone and want to interact -also in truffle oil -mechanisms of olfactory transduction ***KNOW THIS FOR THE FINAL*** -text below is already mentioned above, but it is a narrative of the figure above -odorant binds a GPCR, G protein alpha subunit breaks away and stimulates adenylate cyclase, converting ATP to cAMP, opening a cation channel for passage of sodium and calcium -Calcium then opens up a calcium activated chloride channel, and chloride leaves the olfactory receptor neuron, further depolarizing the cell (IN THE CILIA) -olfactory coding -glomeruli -Starts in the glomeruli -Each glomerulus in the olfactory bulb is tuned to a specific receptor -An olfactory receptor neuron expresses one and only one receptor -No olfactory receptor neurons express more than one receptor -An individual receptor can respond to more than one odor -At the level of the olfactory bulbs the odors are sequestered (segregated) -Much of the processing occurs at the Olfactory Cortex -olfactory receptor genes -approximately 1000 genes in rodents -each olfactory receptor neuron expresses only one olfactory receptor -these same receptors are expressed in the testis on sperm cells -Richard Axel and Linda Buck -Nobel prize in physiology of medicine 2004 -protein must be able to detect a large number of odorants -one gene, multiple combinations (like immunity) -a large family of genes each encoding a different receptor -discovered the odorant receptor gene family (in 1991) -odorant receptor genes -huge gene family -large fraction of our genome (1%) -scattered throughout all of our chromosomes -each odorant gene codes for a protein that is sensitive to a particular chemical structure(s) -slide 37 -olfactory receptor neurons stained just for this single receptor (P2) -Distribution throughout the olfactory epithelium, but all go to a single glomerulus in the OB -olfactory bulb has two halves, symmetry -P2 expressing glomerulus -olfactory receptor neurons are in zones, not random distribution -organization in the olfactory epithelium into zones is matched by similar zoning in the olfactory bulb -~1000 olfactory receptor types -one olfactory receptor type per cell -subset of olfactory receptor types per zone -zone to zone projection -cells of the same type project to a small number of fields (glomeruli) -different odors activate different fields -axons of neurons with the same olfactory receptor converge in the olfactory bulb -a stereotyped map of olfactory receptor inputs in the olfactory bulb -If humans only have 300 receptors, how do we distinguish between 10,000 odors? -See slide 45 -Combinatorial receptor codes for odors -one odorant has multiple "keys" -each key activates a different receptor -the combination of receptors stimulated results in a certain odor sensed by the brain -the common chemical sense (chemisthesis) -importance of chemisthesis -response to irritating, pungent stimuli -activating pain fibers, not specialized receptors, free nerve endings -receptors -short receptor -(<0.1mm) -long receptor -(>0.1mm) -mechanism of transduction -activation of TRP channels -trigeminal chemoreception -heat measured in Scoville units -chili peppers -capsaicin desensitization -Desensitization: After a while you adapt to the burn, and it is not as bad if you keep eating the peppers -if you stop for maybe 10-15 minutes and start eating again, the burn will supposedly be worse than ever -chronic treatment: can damage (but not kill) nerves -neonatal treatment: can kill unmyelinated c fibers, so that when you grow up you can eat the chili fibers and not get the burn -vanilloid receptor 1 (VR1),(TRPV1) -vanilloid-like receptor 1 (VRL-1),(TRPV2) -Capsaicin passes through the phospholipid bilayer and binds to a receptor on cytoplasmic face -opened up by heat and acid -acid burns because of the stimulation of the TRPV1 receptor -cool receptors -TRPM8 -TRPA1 -mustard oil -Δ9-tetrahydrocannabinol -cinnamaldehyde -for more severe pain -respond to marijuana essence -also respond to cinnamon -These receptors are in your mouth AND your nose! -TRPV2 -TRPV1 -TRPV3 -TRPV4 -TRPM8 -TRPA1 -stimulation of nasal trigeminal fibers -associated with painful or irritating chemicals (tingling, stinging, burning) -examples of physiological reflexes to sensing irritating chemicals -decreased respiration -increased nasal secretion -closure of nares and glottis -sneezing -effects of noxious stimulus is minimized and the individual is protected from further exposure -vomeronasal chemoreception and pheromones -pheromones -any chemical or set of chemicals produced by a living organism that transmits a message to other members of the same species -naive response -e.g. pups suckle, males fight, and estrus cycles are altered -their precise nature remains somewhat controversial -A naive animal responds behaviorally to the presence of pheromones without any prior experience or exposure: -conspecific phenomenon, not a learned response -In humans the nature is controversial, we do not have vomeronasal organs -invertebrate pheromones -first discovered in silkworm moths -females secrete a specific blend of odorants that is highly attractive to males -males fly upwind to find the source (as far as a mile away) -vertebrate pheromones -swabbed hamster -a male hamster swabbed with hamster pheromone, "Aphordisin", became sexually attractive to another male hamster -Mice unidentified chemicals in male urine can induce estrous in female mice -Bruce Effect -male urine can induce estrus (heat) in a female mouse -Bruce effect = odor memory -same mouse: pregnancy maintained -new mouse or urine spike with pheromone: pregnancy terminated -the importance of the vomeronasal organ and pheromones -mating behavior -territorial behavior -mice: urine contains a protein which incites other mice to fight -other conspecific behavior -the vomeronasal pathway -vomeronasal organ is located in a pit in the bottom of the nose of the rodent, projecting to a region called the accessory olfactory bulb -from there it goes to other destinations including the amygdala -vomeronasal organ -secondary olfactory system -sensory neurons synapse onto an accessory olfactory bulb -mouse -at base of nasal cavity -responds to bodily fluids introduced into the cavity (non- volatile) -the pheromone detector -main olfactory bulb detects pheromones as well -Most mammals -receptors are not ciliated, have microvilli, look more like receptor cells in taste buds -It is believed in humans our main olfactory bulb is responsible for pheromone sensing because we do not have the vomeronasal organ -behaviors mediated by vomeronasal organ and main olfactory epithelium -pheromone binds G-protein coupled receptor, activated phospholipase C, (PLPC) cleaving into diacylglycerol (DAG) and inositol-triphosphate (IP3), the DAG eventually causes opening of the TRPC2 channel, which opens when calcium comes in and depolarizes the cell -TRPC is important in vomeronasal organs -aggressive behavior -mating partner preference -Essential for successful mating in rodents -Androstenone: male pheromone, released by pigs, also present in truffles (so truffle oil) -Genetic variation in the way we sense androstenone -vocalizations -endocrine effects (e.g. puberty delay, synchronization of estrus) -discrimination of general odors (instrumental conditioning, habituation/dishabituation?) -human pheromones? -anecdotal: man's whisker growth faster in the presence of women -women who live together then to get their period during the same time of the month -chemicals collected from the armpit and dabbed under the nose have the same effect on women -A woman's compounds collected during certain parts of the menstrual cycle will effect other women's menstrual cycles -a chemical taken from a women during one part of the cycle will shorten the menstrual cycle by 1.7 days -a chemical taken from a women during another part of the cycle will lengthen the cycle by 1.4 days -indicates that two pheromones exist -major histocompatibility complex (MHC) -identified as a major component in tissue graft rejection -also appears to influence our body odor -mechanisms for detecting people with similar (or different) genotypes -Based on research, the MHC profiles are such that if you meet a person who has a radically different MHC profile, you are more attracted to that person than you would be if they had a similar MHC profile to yours -human vomeronasal organ? -human fetus -have a vomeronasal organ -connections seem to disappear after ~19 weeks of age -adult -usually a depression (or pit) in the nasal cavity -not always there or on both sides -most human vomeronasal organ receptors are pseudogenes


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