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Lecture 2

PSYC 318 - Week 2 Lecture notes

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PSYC 318
Wayne Sossin

PSYCH 318 Behavioral Neuroscience II Professor Wayne Sossin Week 2, Class 1 Internal Equilibrium First introduced by Claude Bernard in 1860s • French physiologist (1813-1877) • “All of the vital mechanisms, however varied they may be, have always one goal, to maintain the uniformity of the conditions of life in the internal environment…The stability of the internal environment is the condition for the free and independent life”. o Maintaining Homeostasis is critical for life • Thought organisms were composed of simpler parts bathing in an internal fluid/environment. • Walter B. Cannon proposed “Homeostasis” as a designation for the steady states of an organism. o Change in the face of change so as to remain unchanged ▪ So as to maintain a constant internal environment. ▪ Maintaining constancy required action ▪ Constant struggle to maintain balance o Others have proposed mechanisms in the body that detect these losses/gains and initiate compensatory actions. Homeostatic Mechanisms Prototypic features: i. System variable which needs to be controlled o (e.g., body temperature, blood glucose, water balance, CO2 levels) ii. Set-Point o Point at which the variable needs to be maintained iii. Detectors o (Tell the brain whether variable level is too high or low) iv. Correction mechanism o (initiation and cessation) Physiological Thermoregulation: Example: • Body temperature too high • Thermostat/Thermoregulatory centre in hypothalamus activates cooling mechanisms • Includes dilation of blood vessels & Activation of sweat glands o Part of Autonomic Nervous System Reminder: Peripheral Nervous System (PNS): Somatic+ Autonomic nervous system. Somatic Nervous System connects skeletal muscle to CNS. Autonomic Nervous system connects smooth muscl/glands/heart to CNS. Figure also illustrates the Somatic Nervous System response. Thermoregulation: 1. Physiological regulation of body temperature: o Involuntary o This has a limit (You cannot stand in a -30 temperature indefinitely) 2. Behavioural regulation of body temperature: o Triggers conscious decisions in order to preserve thermal balance o Much more powerful than Physiological regulation o Example: Penguins huddle together. ▪ Penguins act like a giant, well-regulated organism. ▪ So effective that penguins risk melting the ice/ Preoptic Area (Thermoregulatory Center) • Part of the Anterior Hypothalamus • Location of the “Thermostat” • Receives input from two sets of receptors: 1. Receptors in the hypothalamus monitor blood (core) temperature (37ºC) 2. Receptors in the skin (somatosensory input) monitor the external temperature Hypothalamus: • Hypothalamus acts in different processes. • Pre-Optic area is involved in thermal regulation. • Located where the optic nerves cross. o Near the Optic Chiasm. o In red on picture. • Initiates behavioral and Physiological thermoregulatory response in reaction to body and external temperature. Not all animals can regulate their body temperaturephysiologically!!! • Endotherms (warm-blooded animals): o Have a fairly constant body temperature (35-40ºC) ▪ e.g. mammals and birds • Ectotherms (cold-blooded animals): o Body temperature changes as the environmental temperature changes (entirely rely on behavioural thermorgulation) ▪ e.g. some vertebrates (fish, amphibians and reptiles) and all invertebrates. Thermal receptors TRP (Transient Receptor Potential) channels: 1. Those that respond to cold located just beneath the epidermis 2. Those that respond to warmth located more deeply in the skin Thermal receptors are members of the TRP family. Seven known families of TRP channels: • TRPV, TRPM and TRPA are important in thermal regulation. Many functions: • Thermoregulation, • Pain (nociseption) • itching, • vision, • smell, • etc.. Diverse activation mechanisms: • Ligand binding • Voltage-gated • G-protein coupled PLC activation (TRPC) • Temperature All Group 1 TRPs have 6 transmembrane TRPMs: domains. • Have a kinase domain at their carboxy-terminus. o Kinase domain can phosphorylate itself A cationic pore is located between domains 5 as well as other proteins (On Serine, and 6. threonine residues). • Permeable to both Calcium and Sodium • Also Hath a TRP domain located carboxy-terminal ions when it’s open. to the 6 transmemrane domain. • Leads to membrane depolarization. • However, it is more seeletive to Calcium TRPAs and TRPVs: ions. • Have anchoring repeats at their n-terminal o When the channel is open, more o Mediate protein-protein interactions. Ca+ flows in that Na+ o Illustrated in green TRPs can be activated using diverse mechanisms: • Ligand binding (Ligand gated) o Menthol binds to TRPM8 channel, interpreted as cooling by the brain • Voltage Gated o React to changes in membrane potential • Some are activated by GProt-coupled PLC activation(TRPC family) Temperature changes. ThermoTRPs • (TRPV, TRPM, TRPA) Thermoregulatory TRPs convert thermal energy (heat) into protein conformational changes leading to channel opening. • Put mice in temperature preference chambers. Two chambers with plaques of different temperature,separated by a door. o TRPM8 knockout mice have an impaired response to cold ▪ Only respond once temperature reaches 15 degrees. o Other Thermo-TRPs KO mice ▪ TRPV-1 deficient mice: no response to noxious heat until temperature reaches 55C. ▪ TRPV-3 deficient mice: Wild Type preferred 35C to Room Temp, KO only slight preference to 35C. ▪ TRPV-4 deficient mice: cannot discriminate between 30 and 34C. Alliesthesia: • Same stimulus produces pleasure or displeasure depending on the thermal body state Process: • Set subjects in a hot or cold water bath. • Subjects then dip hand in another bath. • Rate pleasant/unpleasant. o Subjects in a hot water bath found cold “hand water” to be more pleasant o Subjects in a cold water bath found hot “hand water” to be more pleasant • Homeostasis might be maintained by reward mechanisms. FMRI Study: • Pleasantness of thermal stimuli: o Activation of the mid-orbitofrontal cortex, pregenual cingulate cortex and ventral striatum. • Unpleasantness of the thermal stimuli o Activation of the lateral orbitofrontal cortex Shows a separation of stimuli into different areas of the brain which correlate with pleasant/unpleasant stimuli. Hunger: • What triggers hunger? o Stomach Contractions? Study: • Washburn swallowed balloon which measures stomach contractions • Pressed key each type he feels hungry o Correlation between stomach contractions and hungerpangs. o Stomach controls hunger. ▪ Stomach Empty ▪ Stomach Contracts ▪ Individual Feels Hunger. Problem: • Individuals with stomach surgically removed still report hunger • Hunger regulated by: 1. Glucose 2. Hypothalamus Homeostasis – Blood Glucose • Glucose is the main energy source for our cells. • Normal blood glucose is 5.5mM or 100 mg/100ml. • Low blood glucose levels make us feel hungry. Beta cells: Endocrine cells, release Insulin Alpha cells: Release Glucagon. Has antagonistic effects to Insulin. The key steps leading to glucose-stimulated insulin secretion by β-cells • High Blood glucose • Glucose uptaken by β-cells using Glut 2. o (Glucose transporter) • Glucose enters cell • Glucose converted to ATP by mitochondria • ATP binds ATP-gated K+ channels o Closes channels o Potassium accumulates inside the cell o Membrane is depolarized. • Opening of Voltage-gated Calcium channels o Calcium influx o Stimulates fusion of insulin vesicles with the membrane • Insulin released into the blood stream. The key steps leading to glucose-stimulated glucagon secretion by α-cells • High Glucose levels • Glucose will be up-taken by α-cells. o Happens via Glut1 (SLC2A1 gene) • Converted to ATP in mitochondira. • ATP binds Channels, inactivating them. • Potassium accumulates inside the cell. • Voltage gated calcium channels Close. • Volage gated calcium channels will only open under low glucose conditions. o They are inactivated when the membrane is strongly depolarized. o Only activated in response to moderated depolarization o LOW levels of blood glucose open the channels. ▪ Causes glucagon release. Failure of glucose homeostasis causes Diabetes Mellitus (More than 9 million Canadians affected) • Type 1 diabetes o 5-10% of diabetic patients o Auto-immune destruction of β-cells leading to absolute insulin deficiency o Type 1 diabetics do NOT produce insulin. • Type 2 diabetes o 90-95% of diabetic patients o Insulin resistance and have relative insulin deficiency o Correlates with obesity • Gestational diabetes o Onset during pregnancy Hypothalamus: Center for appetite control • Levels of blood glucose are monitored by receptors located in the periphery o Stomach, liver, intestines, etc. • They send signals (e.g. hormones) to the hypothalamus in the brain to control appetite. Study: • Lesions to the ventromedial hypothalamus (satiety) cause excessive eating in rats. • Lesions to the lateral hypothalamus (hunger) cause reduced food intake . Recap: Important areas for appetite control: • Ventromedial hypothalamus • Lateral hypothalamic nucleus The arcuate center of the hypothalamus (Arc) also plays an important role. Osmoregulation Blood Water Homeostasis • The amount of water in our blood has to remain constant in order to avoid cell damage • Need a balance between: o Amount of water gained (drinks, food, …) and o Amount of water lost (sweating, evaporation, urine,…) • Brain contains osmoreceptor cells (detect changes in blood water) • Sends a message to the pituitary gland to control ADH (anti-diuretic hormone) secretion ADH (vasopressin) • Targets endothelial cells of the collecting ducts of the kidney nephrons o Blood filtering unit of the kidney • ADH causes opening of the water channels (aquaporins) of the endothelial cells (more water reabsorbed from urine) Osmoreceptors in the brain are located in: • Anterior Hypothalamus o Blood-brain barrier, no gaps between blood cells. • OVLT (organum vasculosum of the lamina terminalis): o No blood-brain barrier Circumventricular organs lack the blood-brain area. Osmoreceptors have been found in these areas: • Thirst osmoreceptors located in OVLT as well as subfornical organ (SFO) Limitations of Homeostasis: Homeostasis is not only controlled by physiological mechanisms. 1. Thermoregulation: o Same stimulus may produce pleasure or displeasure depending on the thermal body state 2. Most feeding is unrelated to physiological need o Social factors (eat more in a group), Availability, Variety, Taste o Appetizers increase appetite Goal-Directed Behavior • Mediated by mechanisms unrelated to physiological need Study: Glickman and Schiff (1967) state behavior is mediated by: • Approach toward rewards • Withdrawal from punishments Dalbir Bindra (1978): • Approach positive incentive stimuli o The stimulus has positive value • Withdraw from aversive stimuli o The stimulus has negative value Frederick Toates: 1. Incentive value of stimulus varies with the internal state of our organism 2. Motivational value depends on psychological appraisals unrelated to intrinsic properties o Ex: Food: Easily obtained, bigger or more palatable than expected? 3. Motivational value depends on physiological need o Ex: Food: Blood glucose levels Are there reinforcement / incentive brain mechanisms? o Do mechanisms that regulate interest in motivationally relevant stimuli unrelated to physiological need exist? Study: • Evidence for the existence of reinforcement mechanism. • Stimulate rat brain, observe behavior. • Rat would search with stimulation, stop when stimulation is off. o “This “particular rat,” Milner later wrote, “would advance, sniffing and searching, whenever the stimulation was turned on, and would stop or turn back when it was switched off.” Stimulation was affecting the rat’s behavior. Continued: • Put rat in cage.
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