8/22 Neurotransmission - Glendinning Flashcards
steps in neuron activation
- receive stimuli
- sensory input: pseudouni- and bipolar
- synaptic input: bi- and multipolar
- integrate the input
- APs are activated at trigger zone (area with increased number of Na channels, can initate AP)
resting membrane potential
number
what generates it?
-65mV
- osmotic and electrical forces
- selective permeability
- energy dependent Na/K pump
Na, Cl, Ca (out > in)
K (in > out)
electrical inputs in a nerve cell
neuronal inputs as graded potentials
inputs stimulate or inhibit an action potential
- stimulate: depolarizing (positive, excitatory)
- inhibit: hyperpolarizing (negative, inhibitory)
neuronal inputs are graded potentials → show small changes in RMP in response to inputs
- size of change varies based on strength of input → leads to varied AP firing rate/nt release
EPSP vs IPSP
EPSP: excitatory postsynaptic potential
- depolarizing
- excitatory, graded : usually from opening of Na or Ca channeles
- < 1mV
IPSP: inhibitory postsynaptic potential
- hyperpolarizing
- inhibitory, graded : usually from opening of K or Cl channels
“impact factor”
graded membrane potentials attenuate (weaken) rapidly with distance from start point
“IMPACT FACTOR” depends on:
- location (impact could be greater if stim closer to trigger zone!)
- strength of synapse
4 neuron-to-neuron synapses
AD - axodendritic
AA - axoaxonal
AS - axosomatic
DD - dendrodendritic
summating effection on action potentials
spatial vs. temporal
spatial : number of inputs received summed
temporal : timing of inputs builds up to AP
what’s the point of inhibition/summation?
don’t always want the SAME level of response to an AP! sometimes, want a bigger response than other times
consider:
- postural demands
- environmental changes (ex. terrain)
- goal of movement
combo of excitatory and inhibitory inputs leads to summed state → differential firing rate and force of contraction for diff levels of response
presynaptic inhibition
postsynaptic inhibition
presynaptic inhib:
inhibitory inputs at AXON TERMINALS → selective blocking of synaptic output!
postsynaptic inhib:
inhibiory inputs on POSTSYN NEURON → can inhibit entire neuron
saltatory conduction
axon diameter implications
myelination produces segments of axon that are insulated - CANT trigger AP there
AP instead jumps to successive nodes of Ranvier
greater axon diameter leads to…
- increased conduction velocity!
- higher space constants : signal can move further before decaying
- larger internodal spaces
factors affective conduction velocity
- amt of myelin
- conduction velocity
chemical synaptic transmission
when AP makes it to the axon terminal…
- Ca channels open (Ca influx into terminal) → synaptic vesicles fuse with presynaptic terminal
- nt is released → binds to receptors on postsynaptic membrane
* leads to opening of ion channel!
* *fate of nt released via exocytosis?*
degradation by enzymes, removal by glial cells, reuptake by presyn cell, diffuse away,
two families of postsynaptic receptors
1. ligand gated ion channels
- ionotropic : receptor linked directly to ion channels
- FAST (<1 ms)
2. G protein coupled receptors
-
metabotropic : receptor does not have channel, affects G-protein activation instead
- G-protein dissociates and interacts directly or indirectly with ion channel
- bc of the Gprotein middleman → slower!
- responsible for neuromodulation
major neurotransmitters
excitatory vs inhibitory
PNS
- excitatory : Ach (nicotinic)
CNS
- excitatory : glutamate
- inhibitory : GABA or glycine (spinal cord)
glutamate
major excitatory nt in CNA
- contained in approx 50% of all neurons (virtually all excitatory neurons)
receptors:
ionotropic (excitatory)
ex. AMPA receptor (Na in, K out)
ex. NMDA receptor (Na/Ca in, K out)
ex. kainate
metabotropic (excitatory or inhibitory depending on state of neuron)
NMDA receptor
name
type of gated-ness : how do you open?
role
fun fact: inhibition
N-methyl-D-aspartate receptor
voltage gated AND ligand gated
- NEEDS glutamate AND voltage change
- at RMP/hyperpol, receptor is blocked by Mg
- when depolarized, no Mg block → Na/Ca in, K out → EXCITATORY
- opening of Na/Ca ion channel portion of NMDA potential (when postsyn depol occurs) can lead to long term potentiation (LTP)
role in learning/plasticity AND cytotoxicity
NMDA receptor inhibited by hallucinogenic drugs (PCP and ketamine) → hallucinations that resemble schizophrenia
long term potentiation
example of NMDA
incrased responsiveness of postsyn neurons after repeated stim of neurons (ex. in hippocampus)
ex. NMDA lets in Ca → Ca-dependent signaling cascades →→→ long term potentiation
- insertion of additional AMPA receptors (increased responsiveness)
- changes in dendritic spines
other long term synaptic changes affect:
- devpt of synapses
- regulation of neural circuits
- learning/memory (LTP)
glutamate toxicity
trauma/disease that impairs ATP generation can cause increased Glu release OR decreased Glu reuptake
- Glu NMDA channels allow Ca leak into cells
- increased Ca → inc water update, stim of intracellular enzymes → degradation of proteins/lipids/n.a.s
conditions believed to be assoc: ALS, Alzheimers, tumors, O2 def, ischemia, trauma, repeated seizure
tirpartite synapse
role of glia
close association of presynaptic cell, postsynaptic cell, glial cells
astrocytes (glia) take up nt and excess K at synapses
GABA
type A and B : actions of each
drugs action on them
major inhibitory nt of CNS
GABAA : ionotropic receptors → open Cl channels
GABAB : metabotropic receptors → open K, close Ca channels
drugs that act on GABA : anti-anxiety, hypnotics, anti-epileptics, anesthetics
ascending neurotransmitter systems
mostly neuromodulators
mainly originate in brainstem and project widely
affect: cognition, wakefulness, attn
*target for many psych drugs!
norepinephrine (NE)
projections originate in : LOCUS CERULEUS and LATERAL TEGMENTAL AREA
fx:
- sleep/wakefulness
- attention
- consciousness
- pain modulation
drugs that stimulate NE release:
- amphetamines
- methylphenidate
dopamine
projections originate in : VENTRAL TEGMENTAL AGEA and SUBSTANTIA NIGRA
acetylcholine (ACh)
projections originate in : BASAL FOREBRAIN and PONS
fx:
- arousal
- memory
- nucleus basalic degenerates in Alz disease
endogenous opioids
peptide neurotransmitters
location: spinal cord, brainstem, forebrain
fx: pain, reward
unconventional nts
not stored in synaptic vesicles, not released by exocytosis
- ENDOCANNABINOIDS: excite receptors activated by THC
- lipid metabolites that cross presyn membranes → act as neuromodulators (affect neuronal excitability)
- can decrease transmission of pain, decrease nausea/vomiting
- NO, CO
- gases that permeate plasma membrane
- act through 2nd messenger systems
- might be involved in neurodegen processes
