2/3/17???Synaptic Plasticity (35 mins)- Facilitation:- Potentiation: stim for a longer period of time, duplicates result.o residual Ca build-up: _____- Depression: first input the largest then it goes down. Short in time like facilitation, but opposite.- Long-term Potentiation (minutes to days)- Long term Depression (minutes to days)-------------------------------2/8/17- Skeletal Muscle---------------------------------------SynapsesSound localization (Circuit example used by vertebrates for sound localization)Only if 2 EPSPs arrive at the same time do they sum to reach threshold. - More sound from right ear, then Neuron A will be the only one to sum inputs and reach threshold and neuron will fire. So more sound from the right means more neurons from theleft will fire.o From left, E will be the only one to fire.Lines represent peak of sound pressure.If sound is straight ahead, sound wavesactivated at the same time.Sound sources coming in from right means it will hit right ear before left. Unbelievably efficienct: this circuit is able to break up that 1 μs difference into 45 seconds (can detect 1/45 of a second)- Frequency is coded as position of the long membrane, such that for given frequency you get a maximal vibration of that membrane the hair cell sits. There’s other mechanisms to tune up frequency sensitivity. That frequency sensitivity projects itself onto nucleus so that’s there’s not just one array but thousands in parallel. Each network is very systematically varied in frequency from the one in front and behind it. With distance through the nucleus log. There’s not just one place encoding circuit but there is many of them tuned to a particular frequency and sounds. The outputs of these five neurons go up to another brain center and composition of the sound. How much power is in each band of frequency?Skeletal MuscleContraction is interaction between cross-bridges interacting with thin filaments.Cross-bridge Cycling(Arbitrary how many steps there are)  Cross-bridges (purple) Shaft Binding sites of actin Accessory proteins that attach myosinWhen a prt binds something, it could change the conformation of protein n a conformational way.1) Myosin head is bound to Actin monomer 1. When the myosin head has nothing bound to it, it has high affinity to bind actin. When it binds actin, the angle head is 45°. If all cross bridges are in that state, the muscle is in rigor.2) ATP binds to myosin head and myosin entirely loses its binding affinity to actin. (head detaches) a. RATE LIMITING STEP3) Myosin head has ATPase and will hydrolyze it to ADP and Pi.a. Step 34 is Ca dependent4) The hydrolyzed ATP causes a conformational change in neck and myosin head has 90° angle. (gives precise distance between actin so myosin binds weakly to actin #2, a little more strongly than in step 2)5) The myosin binding to actin lowers the affinity for myosin holding onto Pi, so its released. ~Power stroke where myosin slides over actin6) Release of ADP, rigor state again. Neck/head of myosin molecule- 2 types of schwann cells  one myelinates axons, other sit on top of nerve terminal- Blue=neural terminal- Mitochondria and synaptic vesicles filled with Ach: at crests of folds are nAChR (nicotinic Ach receptor)- Inward current causes large EPSP (aka Endplate Potential)Excitation and Contraction couplingT-tubules / SR= blue (smooth ER of muscle)------------------------------2/10/17-------------------------------T-tubule is continuous with the plasma membrane the lumen is continuous with the extracellular space. V-gated Cl, K channels are in the t-tubule membranes of animals.Na channels in plasma membrane are not uniformly distributed but concentrates in rings around t tubule openings.- High concentration of Na channels. Acts as current amplifier. More inward current by T tubules.- Action potential going down fiber, also go deep into fiber radially.Triad Junction= SR -- t tubule -- SRSR= double walled membrane structure. Wraps around each segment of muscle fiber. Ring of ttubule in every sarcomere.- Lumen of SR is where a is sequestered.- Yellow= t tubule- Ca pumps or SERCA or ryanodine receptor Dihydropyridine receptor: acts like Ca channel, just V-sensor, undergoes structural change when membrane depolarizes. Ca release channel: has lost V-sensitivty. Ca comes out when open. The two are linked through proteins, Dihydropyrdine yanks the proteins and opens the Ca channel.For every AP, a burst of Ca comes out, The rise in Ca is brief because:- Ca pumps constantly working to pump Ca back in- 2 Ca buffering proteins in cytoplasm: porvalbumin, calmodulinTroponin/tropomyosin: regulated contraction through CaTroponin complex has 3 types:- Troponin C- Ca binds and moves troponin I out of the way to expose site to actin- Troponin T- binds to myosin.- Troponin I- inhibits, binds to actin (blocks binding site on actin), shifts over when TnC binds Ca Diagnositic tool: ammunoassay for cardiac troponin is a standard test for cardiac infarction. Troponin found in blood= sign of muscle tissue deadIsometric contraction: constant length- If you stimulate short muscle, you won’t get much force, as you stretch you get more and more force. Overstretch it will fall off.- Muscle generates force by having overlap between thick and thin filaments.- A muscle contracts, the muscle fibers generate force (contraction with shortening), or if too heavy will - When the muscle contract against a heavy load=…….- Force length relationship curve: L0= length at which you get maximal force at isometric contraction. Upside down U-shaped curveMuscles increase in size, but sarcomeres are the same length. When in resting position, the average sarcomere length is at zero (no matter the age). Therefore, sarcomeres must be added throughout growth to maintain this?- Load=force- No force=no velocity.- Isometric contraction when force muscle is generating is the same as the load (being opposed by the exact same force).- Lengthening is a negative change in.- When you contract a muscle and it shortens= concentric, elongates= eccentricProperties Used to Classify Muscle Fibers:1. Whether ion channels in sarcolemma allow action potentials (all-or-none twitch) or not (graded or tonic contractions).  Twitch?2. Rate of cross-bridge detachment during contraction, related to ATPase activity of myosin isoform. Determines V0.  How fast can the muscle build up force?3. Number of Ca2+-pumps in SR,