Neuroscience Chapter 4

intracellular signal transduction

NT, paracrines, and hormones

3 components: ligand, receptor, effector

part inside the cell

advantages of chemical signaling

1. signal amplification

2. precise control of behavior over time

activation of signaling pathways

3 classes

cell-impermeant: receptors on plasma membrane, travel far, short-lived by metabolism or endocytosis

cell-permeant: receptor inside cell, carrier proteins, long lasting

cell-associated: found on outer plasma membrane, only interact with adjacent cells

receptor types

A. Ligand gated: open/close

B. Enzyme-linked: usually kinases(tyrosine), intracellular target proteins

C. G-Protein coupled: metabotropic

Intracellular: regulates gene transcription

G-Proteins

heterotrimeric: activation

monomeric: (GEF)

inactivation

downstream effectors/enzyme 2nd messengers

bind and activate ion channels

second messengers/calcium

concentration gradients

Ca/calmodulin-dependent protein kinase type II: substrates are ion channels and intracellular signal transduction protiens

cAMP/cGMP

both bind gated ion channels important in phototransduction and sensory transduction: olfaction

Phosphatases

Protein Phosphatase 1:(PKA) affects K and Ca channels as well as AMPA and NMDA type glutamate receptors

Protein Phosphatase 2A: most abundant in brain. affects Tau(microtubules in axon). Alteration in activity seen in neurodegenerative diseases(Alz), cancer, and diabetes

Protein Phosphatase 2B(calcineurin): controlled by Ca/calmodulin. Target is NFAT(transcriptional regulator in nervous system development) and ion channels

CREB

transcription activator. activated by PO4

Regulated genes are c-fos(transcription factor for delayed genes), BDNF, tyrosine hydroxylase(needed for synthesis of catecholamines), and some neuropeptides

synaptic plasticity

changes in the strength of signaling at a synapse

can be over the short term of long term

can increase or decrease strength of signaling

synaptic facilitation: increase in synaptic strength when 2 or more APs hit within milliseconds of each other

synaptic depression: decrease in synaptic strength

short term plasticity

facilitation: presynaptic calcium is not able to be pumped out before the next AP arrives

depression: caused by a depletion of synaptic vesicles available for release

post-tetanic potentiation

synaptic strength remains high for a long period(minutes) after a brief series of signals(tetanus)

long term synaptic potentiation

learning and memory: hippocampus

requires temporal summation to remove Mg from NMDA

leads to increase in AMPA receptors

long term synaptic depression

weakens synapses

purkinje fibers in cerebellum, parallel fibers, and climbing fibers

AMPA receptor and metabotropic receptor produce a small local depolarization

climbing fibers cause large depolarization triggering voltage gated channels

leads to decrease in AMPA receptors