Module 6 - Neural Control of Homeostasis Flashcards

Question

L6.6 - Explain the impact of sleep restriction/loss on brain function

Answer 1

Sleep deprivation leads to decreased performance due to failing concentration and your ability to judge your own performance drops as well. We observe a plateau in learning motor skills with disturbed sleep and a decrease in creativity with loss of REM sleep. 3 days of insufficient sleep make a significant difference from 6 to 8 hours. Memory formation might be impacted, and your brain won’t be “cleaned” as well by the glymphatic system (acumination of waste produces) The postsynaptic density might shrink during sleep to promote learning when waking up.

Answer 2

EEG is generated by the dipoles in neurons. The fact that the pyramidal neurons in the cortex are placed in parallel enables their dipoles to be stronger and send out a higher electrical signal. We measure post synaptic potential and not APs

Answer 3

Delta: deep sleep - 1-3 hz (look like mountains) Theta: early sleep - 4-7 hz Alpha: awake but relaxed - alpha 8-13 hz Beta: awake and focused - 14-24 hz Gamma - 25+ hz (squiculy lines) You have sleep spindles (for memory consolidation) and k-complexes (shows if we’re being disturbed during sleep) in N2.

Answer 4

It's a balance between energy in and out (E_in – E_out = delta stored energy) – classic way of thinking. If you go a little over one day, it might even out another (homeostatic control). Problem: we don’t have the same metabolism or take up the same number of calories – 2-10% goes through without uptake. Another problem: it implies that you’re responsible for your weight – the body doesn't correct everything. There is some decision making, but your homeostatic processes will influence you (you will be hungry when cutting calories). 40-60% is genetically determined - almost all genes associated with obesity was in the brain  points to obesity being a brain disease. There is a zone of indifference for homeostasis (around 10)  we might all have a different homeostatis setpoint?

Answer 5

Neuroendocrine signals can be sensed by the brain in the adipose (leptin) and sensed in the hypothalamus, where leptin inhibits ARPG and excites POMC. Some work on bone/muscle signaling or from signals in the liver. Signals from the gut can also decrease food-intake. In the arcuate nucleus, AGRP/NYP code for hunger (when inhibited the PVN is disinhibited and we stop eating) and POMC neurons will signal for weightloss when activated.’ Leptin comes from adipose tissue and stops eating through AGRP and LHA inhibition and POMC excitation. POMC will excite the PVN to signal to the NTS, which decreases food intake. Ghrelin come from the stomach and activates AGRP/NYP while inhibiting POMC to increase food intake. It also has effects on the reward system (VTA  Nucleus accumbence), which normally interacts with the LHA, what also signals for eating.

Answer 6

The arcuate nucleus (in the hypothalamus) signal to the lateral hypothalamus to start eating and paraventricular nucleus for stop (both when excited). Leptin has receptors in both (blocks one and promotes another). Leptin is a long-term stop-eat signal. VTA to NAc are connected to the lateral hyp (active when we eat) --> problem is that the endogenous hormones have to penetrate the BBB, so effectiveness is debated POMC are activated by leptin and inhibit AGRP and increases NTS signaling to stop food intake. we don't know how this works

Answer 7

AGRP neurons would be great to target (inhibit) as they fire for hunger The NMDA receptors are highly involved in obesity – we want to antagonize NMDA receptors (ketamine helps lose 3% body weight over time) – memantine (for AD – also an NMDA antagonist) helps a lot in weightless By combining appetite lowering gut peptides (GLP1) with a small-molecule (NMDA antagonist) through a chemical linker  idea was to inhibit food want and need. The NMDA antagonist would target the NTS and the peptide the hypothalamus  very effective  lowers the insulin level

Answer 8

LH and FSH are release from the pituitary in response to the hypothalamic release of GnRH  triggers the gonads (ovaries or testes) to release either estrogen/progestogen or testosterone. Both have a feedback mechanism to the hypothalamus, but the female system is more complex, as the presence of estrogen leads to more LH and FSH release to mediate ovulation during the menstrual cycle. Males work on a 24-hour sex-hormone cycle (peak in morning and decrease over the day), where the female one is 28 days (estrogen high around ovulation and progesterone increase between ovulation and menstruation).

Answer 9

What is puperty?: Primary changes = increase of hormones and secondary changes = physical changes They might be linked, but not fully, as secondary changes are occurring a year earlier (perhaps due to obesity?). We see a correlation, but there is not a linear curve. What triggers puberty: We don’t really know. Both weight increase and steroids can help trigger puberty onset, but neither are sufficient alone The kisspeptin might be important in inducing puberty, specifically because it activates GnRH release. Neurons with it’s receptor (Kiss1) is found in the AV-PVN and arcuate nucleus and signal to the GnRH neurons for GnRH release. When knocking out kisspeptin, animals don’t sexually mature It seems that while the receptor is always there, kisspeptin will increase during puperty to trigger activation It seems that kisspeptin might be inhibited in the arcuate nucleus during childhood, but as puberty start, the Kiss1Rs become less sensitive to the inhibition and kisspeptin in the AV-PVN triggers GnRH release with the disinhibited arcuate nucleus.

Answer 10

Sexual dimorphism is the systematic difference in form between individuals of different sex in the same species

Answer 11

The SRY (sex reversal gene on the Y chromosome) gene on the Y chromosome allows men to develop differently from women. It’s not expressed in the brain. In the motor cortex will have different projections in males/females to accommodate different genitalia Females have far more neurons in the AV-PVn than males to control the menstrual cycle (there are higher kisspeptin levels) – their projections differ too. In contrast, male rats have a larger sexually dimorphic nucleus of the preoptic area (SDN-POA). zebra finch brain - the male sings and the female can't, as she doesn't have the right neurons in the brain (missing area x) the Tobaco hawk moth male has larger antenna, and the female has the ability to smell tobacco plant where she lays eggs. The male moth can sense smalls levels of female pheromones (males have macroglomerular complex in their brain) Males have larger Sexual dimorphic nuclei in the POA (structural), but females have more kisspeptin neurons in this area Antero ventral preoptic area (AVPA) (functional)

Answer 12

The mechanisms behind the dimorphism seem to be mediated by both genetic and hormonal differences. The SKY gene enables a peak in testosterone during week 15 of development, which sex-sensitive neurons in the brain can convert into estradiol through the enzyme aromatase. Estradiol will agonize its receptors and cause downstream effects such as changes to neurotransmission and membrane permeability, but also modulation of transcription

Answer 13

Our core temperature will remain the same, but the shell (outer limbs) will vary. We can increase heat by brown fat thermogenesis, muscle shivering, goose bumps and skin vasoconstriction (to keep the heat to the core). We can cool down by sweating or by skin vasodilation. Most of these processes are mediated by the sympathetic system (Brown fat thermogenesis, vasoconstriction, sweating) and others the motor system (shivering) Brown fat thermogenesis happens when norepinephrine binds to receptors on brown fat cells. Here it activates UCP1 in the mitochondria and increases the proton leak, leading to increased heat production and thermogenesis

Answer 14

Temperature homeostasis is regulated by the POA in the hypothalamus. POA receives information from temperature sensitive fibers located in the skin, viscera, spinal cord and brain (responsible for temperature sensing). Here TRP-receptors are temperature gated ion channels and will open for different temperatures. TRP-A1 is for noxious cold, TRP-M8 is for cold (and mint), TRP-V3 or TRP-V4 is for sensing warmth and TRP-V1 and TRP-M3 for noxious heat (V1 also for capsaicin). The TRP channels signal through the anterolateral tract, but can also trigger reflexes to e.g., withdraw hand from a hot plate. POA sends signals for temperature adjustments to brown fat, muscle, blood vessels (effector organs). TRP receptor continuum: 0 degrees: noxious cold max 10-20 degrees: noxious cold active 20-30 degrees: cold sensing max 40-43: warm sensing max 43: noxious warm activated 45-53: noxious warm peak