Synaptic Transmission II and Mol Bio of Presynaptic

Synaptic Transmission II and Mol. Bio of Presynaptic Terminal Lectures 9 and 10 Rachel A. Kaplan and Jeongmin Kim

Announcements • If you’re interested in the material we’ll be covering today, I HIGHLY recommend Julie Kauer’s class Synaptic Transmission and Plasticity – Also Neuropharmacology • Keep up with the material, good work on exam 1! – Feedback about the short answer?

Roadmap • Part 1: Mechanisms of Release • Part 2: Quantal hypothesis of neurotransmitter release • Part 3: Vesicle hypothesis of neurotransmitter release

I: MECHANISMS OF RELEASE

Presynaptic Ca 2+ is necessary and sufficient for NT release • Blocking Na+ with TTX blocks presynaptic APs – No AP = No depolarization = no NT release – Depolarize to 40 m. V with TTX, get NT release • ∴ Na+ is not responsible • Blocking Na+, K+ currents, Ca 2+ currents are still present during depolarization – NT released! – Clamp at ECa 2+, no more Ca 2+ influx, no more NT release • ∴ Ca 2+ is necessary and sufficient for NT release

If you’re interested, more on Ca 2+ is coming up in the course! • Read Fernandez-Chacon et al. 2001 on Synaptotagmin I – the calcium sensor! – http: //www. nature. com. revproxy. brown. edu/nat ure/journal/v 410/n 6824/pdf/410041 a 0. pdf – This work won a nobel prize – I’d love to discuss it with you – I think this is a great paper

Ca 2+ enters terminal through VGCa 2+ channels • In PNS (end plate) – VGCC are located directly opposite ACh. C • This is because VGCCs are located VERY closely to docked vesicles, so that Ca 2+ = ACh release ACh. C activation (efficient response) • In CNS – Very similar to above, though different NTs

II: QUANTAL HYPOTHESIS

Minis (m. EPPs) are the building blocks of the EPSP (EPP) • Observed: – Minis are all the same size – Have the same shape as EPSPs • Hypothesized: – Lots of minis together = EPP – m= Vavg/q – Their release should follow Poisson

Please try to fully understand this equation and its variables. • Quantal content (m) – Number of quanta released • Mean EPP size (Vavg) – The total amount of depolarization • m. EPP, or quantal size (q) – The amount of depolarization of one quanta m= Vavg/q

Empirical mini release in CNS follows Poisson distribution which suggests statistical model is correct. • If probability of a single event is unlikely, then the probability of multiple occurrences of an event is less and less likely.

In high release probability synapses, mini release follows binomial distribution. • m=np – m= quantal content • Can be 1 in certain synapses (i. e. 1 vesicle saturates all post receptors) • Reflects # postsynaptic receptors that respond to the NT released – n = quanta available for release – p = average release probability

III: VESICLE HYPOTHESIS

Quanta described in quantal hypothesis are vesicles! • Slam-freezing is a techinque that allows for visualization of vesicles in the act of fusing – “omega shapes” • # Pits in membrane = Quantal Content – Therefore quanta = vesicles