Neurobiology Ch. 8 PDF

Ch 8. Motor & Regulatory Systems 8. 1) Muscle contraction : Muscle cells contain myofibrils longitudinal -...

Ch 8. Motor & Regulatory Systems 8. 1) Muscle contraction : Muscle cells contain myofibrils longitudinal - which are thread-like structures - Myofibrils consist of sarcomeres which are units of thick thin filaments & · Thin filaments : F-actin The sliding of thick thin filaments mediated by the · Thick filaments : myosin interactions of actin myosin causes muscle contraction F-aktin binding motor protein Myosin head has an ATPase domain which hydrolyze ATP - can When the myosin head interacts w/ actin , it converts chemical energy from ATP hydrolysis into - mechanical force in the form of a power stroke N this is how the filaments move rythmatically - Cat is also needed W/ ATP. This is bk the F-actin in the thin filaments is coated wh 2 proteins called tropomyosin E troponin. An increase in Cast changes the actin-tropomyosin complex which exposes the actin surface that interacts w/ myosin - cat controls how muscle contract , excitation-contraction coupling : 1.) When a motor neuron sends a signal to the neuromuscular junction , it releases ACh 2 ) Ach attaches to the muscle cell channels that let ions in which. receptors on , opening , causes the muscle cell to get depolarized 3 ) This. depolarization spreads throughout the muscle cell triggers sarcoplasmic reticulum to release Ca2t 4.) The cast causes all parts of the muscle cell to contract at the same time. 5 ) The sarcoplasmic reticulum then quickly takes the Cast back so the muscle can get ready for the next signal. 4) chained reflex feedback 8 hypothesis : 1) the spinal cord wh intact sensory is enough for rhythmic activation of muscles (TRUE) 2) when sensory feedback is prevented then rhymthic activation of muscles stops (FALSE) Experimental Evidence : · In this experiment , researchers studied how the Spinal cord controls muscle contractions in the legs of an anesthetized Cat. All leg muscles were surgically inactivated except for one pair : the extensor the flexor. This way , the movement of those 2 muscles could be focused on. They cut the spinal cord above the segments controlling the hindlimb. Surprisingly , this caused the extensor & flexor to move rhythmically , similar to a walking manner , even though the brain was no longer sending Signals. Then , they cut the sensory nerves (dorsal roots) to stop any feedback from the muscles to the Spinal cord. Even wout sensory input , the muscles still moved rhythmically. This experiment supports hypothesis 1. · An incision was made at the level of the midbrain of a cat so that the cerebral cortex/thalamus and brainstem/spinal cord are disconnected. The cat could no longer control its movement but was still able to walk on a treadmill after brainstem stimulation. The contractions of muscles during the walk were recorded by their action potential patterns in electromyograms. The muscles worked the wh nothing changing. Spinal still wout same way This means the cord can control stepping needing signals from the muscles. - Central Pattern Generator (CPG) : CNS circuit that can produce rhythmic output for coordinated contraction of different muscles without sensory Feedback M In the and cat experiment , sensory feedback produced by increasing the speed of the treadmill regulate the speed of the stepping cycle & trigger the transition of motor patterns from walking to galloping , etc. 8 5) What's. being studied ? scientists studied a small group of in crustaceans understand how - neurons to rhythmic movements , such as stomach contractions , are controlled. This rhythm is called the pyloric rhythm. ~ caused by STG's Neurons involved : of hyperpolarized blc of the inactivation voltage - interneuron AB (pacemaker) gated cation channels delayed I channels - one : or - three motor neurons : PD , LP , E PY which control different stomach muscles How it works : - AB is the pacemaker : it naturally fires in a rhythmic pattern (depolarizing to fire , and hyperpolarizing to rest) without needing input from other neurons - This rhythmic firing is due to its specific ion channels , which opend close in a cycle to cause firing and resting Neuron interactions : - AB&PD are in Sync : they fire together bi they are connected by gap junctions - ABEPD inhibit LP & PY : When ABG PD fire , they keep LP & PY from firing LP & PY inhibit each other Once AB PD firing LP fires first which delays PY from firing - : Stop , The 3 phase rhythm : & 1) AB/PD fire together , inhibiting LP and PY LP receives less inhibition so it expresses ) LP fires PY ABIPD Kt channels & hyperpolarization 2. next , inhibiting and less more 3) PY fires last LP and restarting AB/PD activated cation channels , stopping Important : - This rhythm happens automatically , even without sensory input , because of the built-in connections & properties of the neurons in the STG. The AB neuron drives the rhythm , while the interactions between all 4 neurons ensures a coordinated cycle of firing. Pacemaker Cell : type of neuron or muscle cell that can create rhythmic electrical signals w/out any input from other cells. b) The spinal 8 cord uses multiple CPG's to control locomotion - Vertebrate CPG's : located in the Spinal cord & control complex limb and body movements - Extensor & Flexor muscles : · movement requires alternating contraction of extensors (straighten joints) and flexors (bend joints · Extensor flexor motor neurons are activated alternatively via mutual inhibition of their premotor circuits - Each limb has its own CPG network , which coordinates flexor-extensor pairs at different joints - Multi-Limb Coordination for Locomotion Walking : · Limbs more out of sync · Hopping/Galloping : Limbs on both sides Synchronize This involves switching from mutual inhibition to mutual excitation between left and - right limb - The VO interneuron study in mice : Goal : Investigate the role of VO interneurons in left-right limb alternation during walking Method : Vo interneurons (from Dbx1 progenitors) were selectively destroyed using genetic engineering · Dbx1-cre mice : Express fre recombinase in VO interneurons DTA diphtheria VO · mice : Cre activates toxin , Killing interneurons Breeding these mice created transgenic mice lacking VO interneurons walked normally left right limbs Results : Normal mice I wh alternating VO-Ablated mice > Hopped instead walked wh left right limbs in sync Spinal Cord Recordings : Normal mice < left right neurons alternated firing in a rhythmic pattern Transgenic mice < left right neurons fired in Sync V Flexor and extensor Different CPG's for flexor/extensor L muscles remained intact and for left/right alternation VO interneuron subtypes : - Inhibitory VO interneurons = low speeds Excitatory VO interneurons high speeds - = · As locomotion speed changes , different subpopulations of CPG neurons are activated and deactivated Ex.) Zebrafish experiment -Slow Swimming : A specific set of interneurons is activated - Fast Swimming : Low speed neurons turn off , and new neurons become active * Motor neurons are different b/ smaller neurons remain active even when larger ones are recruited - Neurons for rapid Swimming mature first so zebrafish can escape predators early in life 8 a) The basal ganglia participate in initiation and selection of motor programs. V difficulty initiating also called cerebral nuclei movement M - 2 disorders that affect the basal ganglia are Parkinson's disease and Huntington's ~ excessive disease movement V balances excitation of DP and inhibition of Role of SNc : regulator that I · SNC releases dopamine , which modulates activity of the 2 pathways in the basal ganglia Direct pathway (D1 receptors) Dopamine causing : excites these movement neurons - , Indirect pathway (D2 receptors) Dopamine : inhibits these neurons , reducing movement - Direct pathway mechanism : Dopamine from SNC excites D1 neurons in the striatum - This reduces ganglia output (GPi/SNr) - activity in the basal Centers which are normally active and suppress motor centers in the thalamus brainstem - Reduced GPi/SNr activity enables movement initiation Evidence show that D1 GPi/SNr activity and : Optogenetics activating neurons decreases enhances locomotion in mice Indirect pathway mechanism : Dopamine from SNC inhibits D2 in the striatum - neurons - This reduces the indirect pathway's activity , which increases GPi/SNr output and suppresses movement Evidence : Optogenetics experiments show that activating D2 neurons increases GPi/SNr activity which suppresses locomotion in mice the · Both pathways are activated at same time during voluntary movement Direct pathway specific - : initiates motor programs Indirect pathway : competing or unwanted movements - Suppresses Evidence from Ca imaging : -During specific motor tasks , activation of both pathways was observed This dual activation ensures precision in program selection prevents interference - motor from unwanted movements. 19) Circadian 8 Rhythm V adaptation to Earth's 24 hour light-dark cycle caused by its rotations - Circadian rhythms persist even without light cues · Mice in constant darkness remain active during "subjective night" , showing the existence of an internal clock The Biological Clock : Seymour Benzer identified the Period (Perl fruit flies via in genetic screening - gene · Mutations in Per could speed up , slow down , or eliminate circadian rhythms · Deletion of Clock gene could seriously impair circadian rhythm Mechanism of Circadian Rhythm : 1) CLOCK (partnered w/ CYC in flies or BMAL1 in mammals) binds DNA to activate PER and related gene transcription 2) PER/TIM (fly) or PER/CRY (mammals) proteins are produced 3) These proteins form complexes that enter the nucleus & Inhibit CLOCK/BMAL1 , suppressing their own transcription and activating other genes for circadian rhythm 4) This suppression lowers PER protein levels , relieving inhibition and restarting the cycle ↑ rhythmic that with light/dark cycles gene expression aligns · Period mRNA levels cycle over 24 hours , rising and falling in a circadian fashion · High PER protein inhibits its transcription , creating oscillatory gene expression - controls phosphorylation , nuclear entry , and protein degradation Band Feedback loop regulates BMALL , adding strength -regulate a good amount of genes in flies & mammals All cells exhibit circadian - cycles Ex) mammalian fibroblasts in culture Sustain circadian expression gene & different - Plants fungi use similar Feedback loops with proteins Raster of plots show the timing period circadian rhythm -. 21) Circadian Rhythms 8 & SCN SCN for Circadian rhythms - = master clock in mammals - Synchronizes rhythms E links them to environmental light Cycles If SCN damaged it disrupts circadian behavior but it can be restored with - is , transplanted fetal SCN +issues Experimental Evidence : · In golden hamsters, a mutation called Tau shortened their circadian rhythms L > 22 hours 20 hours for for heterozygous homozygous When SCN +issue from Tal mutants was transplanted to SCN-lesioned wild-type hosts, the restored rhythm matched the shorter time period Wild type SCN Tissue SCN Wild type hosts , shorter rhythms Light Mechanism : SCN receives light input via iPRGC's in the retina - - Light triggers glutamate release from ipRGC's onto SCN neurons , leading to : Activation of · glutamate receptors clock gene · Increased Catt transcription - · Phosphorylation of CREB , which activates PER1 and PER2 Mammals : transcriptional regulation Flies : post-transcriptional mechanisms SCN's unique properties : Circadian pacemaker neurons : SCN oscillate electrically in circadian cycles, - neurons regulation of + even when isolated , due to K channels Highly interconnected through gap junctions & Neuropeptide Signaling - · SCN sends rhythmic signals to other hypothalamic nuclei , influencing : The PVH which controls - , autonomic outputs Temperature regulating centers producing daily body temp - ,. Cycles Slow at 4 : 30 am , high at 7 00: pm) CRM controlling glucocorticoid production circadian patterns - neurons , in * Clocks in other parts of the body, like the liver, can be reset by eating at certain times 8 22) Sleep & in mammals across the animal Kingdom sleep stages. · Sleep in non-mammalian species : -sleep is identified by certain behaviors 1. ) Decreased responsiveness to sensoryStimuli 2) Sleep deprivation results in increased sleep afterwards (sleep rebound 3) Sleep & wakefulness follow patterns dictated by the organism's internal biological clock Ex ) Fruit flies. in their sleep state : - Exhibit bouts of inactivity Adapt specific postures - showed reduced - arousal to stimuli Demonstrate homeostatic regulation (when sleep deprived , they experience sleep rebound - sleep in mammals : · sleep and its stages in mammals are measured using EEG z measures electrical activity in neurons using electrodes · EEG patterns during sleep state high frequency low-amplitude oscillations : Waking - , NREM sleep : low frequency high-amplitude oscillations - , ↓ as sleep deepens REM Sleep : low-amplitudeOscillations (vivid high frequency dreaming - , ↓ rapid eye movements & full muscle relaxation  · sleep cycles : Humans REM - alternate between NREM and sleep multiple times per night · A typical cycle lasts 90 minutes - Light NREM sleep < Deep NREM sleep > REM sleep Repeats before waking up · Adults spend 25 % in REM sleep and infants spend 80 % Neural mechanisms of sleep NREM sleep < synchronized , rhythmic oscillations in its EEG patterns L ~ connections long-range input in cortex from thalamus · Thalamus : contains pacemaker cells that produce rhythmic activity without input from other cells waking & REM sleep EEG patterns · Instead of being synchronized , the brain shifts to asynchronous firing ? why input from world activity - Sensory the alters brain adjust activity support alertness REM - Chemical messengers neuron to or sleep 8 23) Mammalian sleep-wake cycle regulation. 2 key systems in wakefulness E sleep regulating : - f 1) Ascending arousal System > keeps brain awake & alert -Basal Forebrain & Tegmental Areas key components : a - Cholinergic Neurons < promote activity in the thalamus cortex to maintain wakefulness and active brain state serotonin , histamine , and norepinephrine A G · - Monoamine Neurons Active during wakefulness but less active during Lateral Hypothalamus NREME REM sleep T Hypocretin/Orexin Neurons > uses hypocretin to awake - stay Connects · to first 2 neuron systems which activates AAS 2). Sleep-Active System