Neurotransmission (Glendinning) Flashcards
What is a graded potential?
Describe the molecular processes that underlie graded potentials.
Changes in membrane potential that vary w size of input, as opposed to being all-or-none. Graded potentials are SUMMED (excitatory + inhibitory)
- ~10 mV to reach threshold -> If reached, AP is triggered.
- AP FIRING RATE and NEUROTRANSMITTER RELEASE vary depending on strength of synapse and location (i.e. whether stimulation happens at synapse vs. dendritic tree)
Explain spatial and temporal summation and describe its importance in neural processing.
Spatial summation: number of inputs received
Temporal summation: timing of those inputs
Describe the molecular processes that underlie action potentials.
- At chemical synapses, chemical neurotransmitter molecules, stored mainly in synaptic vesicles, are released from presynaptic terminals
- Bind to NTM receptors on postsynaptic neuron -> give rise to either excitation or inhibition of postsynaptic neuron
- When excitatory synaptic inputs are sufficient to excite a neuron, AP occurs -> travel rapidly throughout length of neuron
Describe the molecular processes that underlie action potentials.
- Depolarization
- Fast activation of Na+ channels
- Slower activation of K+ channels (during refractory period, cannot have another AP) - Repolarization
APs triggered at successive regions of the axon (recently depolarized regions become refractory)
Explain the pre- and post-synaptic events that occur within a synapse.
- At chemical synapses, chemical neurotransmitter molecules, stored mainly in synaptic vesicles
- AP invades presynaptic terminal
- Depolarization of presynaptic terminal causes opening of voltage-gated calcium channels
- influx of calcium through channels
- calcium causes vesicles to fuse w/ presynaptic membrane
- transmitter released into synaptic cleft via exocytosis
- Bind to NTM receptors on postsynaptic neuron
- opening or closing of postsynaptic channels -> give rise to either excitation or inhibition of postsynaptic neuron
- removal of NTM by glial uptake or enzymatic degradation
- Retrieval of vesicular membrane from plasma membrane
Distinguish between ionotropic and metabotropic post-synaptic neurotransmitter receptors.
Ionotropic: NTM receptor linked directly to ion channels - v fast ( positive/negative ions can go through the open channel (channel could be closed too… takeaway: CONFORMATIONAL CHANGE OCCURS)
- FAST EPSP
i. e. fast knee jerk reflex
Metabotropic: receptor does NOT have channel - G protein activation: NTM binds G-protein receptor –> G-protein dissociates and interacts directly or indirectly w ion channel
- Responsible for NEUROMODULATION (long term changes in post-synaptic neuron or might modulate fast neurotransmission)
- SLOW EPSP
Describe the major receptor types for the neurotransmitters glutamate and GABA.
Major excitatory neurotransmitter
- in PNS: ACh (nicotinic)
- in CNS: glutamate
More on glutamate:
- contained in approx 50% of all neurons (and virtually all excitatory neurons)
- most central glutamate synapses use both AMPA and NMDA (N-methyl-D-aspartate) IONOTROPIC receptors
- AMPA: allow excitatory current to come in carried by sodium… Potassium also leaves so AMPA opens both sodium and potassium
Major inhibitor neurotransmitter
- in CNS: GABA or glycine (spinal cord)
More on GABA:
- GABA (A) ionotropic receptors open Cl- channels (inhibitory)
- GABA (B) metabotropic receptors open K+ or close Ca2+ channels
- drugs that act on this channel*: anti-anxiety, hypnotics, anti-epileptics, anesthetics, alcohol
Discuss the characteristics and significance of the NMDA receptor.
NMDA - same as AMPA + also allows calcium to enter (both voltage-gated and ligand-gated aka needs both depolarization AND glutamate… at resting membrane potential, receptor is blocked by Mg2+)
Depolarization causes Mg2+ ion to pop out of receptor and sodium and calcium can enter/potassium can exit
Calcium entering is imp for LONG TERM POTENTIATION (neuron will be more responsive the next time you receive that input - learning or forming a memory) –> inc. intracellular Ca2+ activates Ca-dependent signaling cascades –> insertion of more AMPA receptors on postsynaptic neuron –> increased glutamate signal –> inc. memory
Note: NMDA receptor inhibited by hallucinogenic drugs PCP - “angel dust” and ketamine. Blocking NMDA receptors produce hallucinations -> resemble schizophrenia
Define excitotoxicity and describe the role of glutamate in cell death.
Too much of a good thing!
Trauma/disease that impair ATP-generation can cause increased glutamate release OR decreased glutamate reuptake by astrocytes
- glutamate NMDA channels allow Ca2+ to leak into cells
- inc. Ca2+ causes inc. water uptake, stimulation of intracellular enzymes that degrade proteins, lipids, and nucleic acids (aka neurons will end up self digesting)
Examples of conditions thought to be associated w/ GT:
- ALS
- Alzheimers
- O2 deficiency
- Ischemia
- Trauma
- Tumors
- Repeated seizures
Explain what is meant by neuromodulator and list the major neuromodulators in the human brain.
neuromodulators are a subset of neurotransmitters - effect occurs in diffuse manner b/c of volume exposure
mainly originate in brainstem and project WIDELY
affect cognition, wakefulness, attention, etc…
target for many psychiatric drugs
NOREPI
- Projections originate in LOCUS CERULEUS and LATERAL TEGMENTAL AREA (of brainstem)
- Functions: sleep, wakefulness, attention, consciousness, pain modulation
- Drugs that stimulate NE release: amphetamines (speed) and methylphedinate (ritalin) - ADHD patients take this to improve attn
DOPAMINE
- Projections originate in VENTRAL TEGMENTAL AREA and SUBSTANTIA NIGRA (midbrain)
- Nigrostriatal pathway: control of movement (parkinson’s)
- Mesolimbic pathway: reward (addiction), schizophrenia, depression
- Mesocortical pathway: working memory, schizophrenia (negative signs)
ACETYLCHOLINE
- Projections originate in basal FOREBRAIN and PONS
- Functions: arousal, memory
- Nucleus basalis degenerates in alzheimers (ACh decreases)
ENDOGENOUS OPIOIDS - peptide NTM
- located in spinal cord, brainstem, forebrain
- Functions: pain and reward
ENDOCANNABINOIDS* (unconventional - not stored in synaptic vesicles or released by exocytosis)
- Excite receptors also activated by THC (active ingredient in marijuana)
- Lipid metabolites that cross presynaptic membranes (act as neuromodulators)
NITRIC OXIDE and CARBON MONOXIDE
- Gases that permeate plasma membrane
- Actions are through 2nd messengers
- may be involved in neurodegenerative processes
List two diseases related to demyelination
MS
- autoimmune
- oligodendroglial myelin attacked (Slower CV due to demyelination)
- CNS
GBS
- viral infection (1-2 weeks after)
- demyelination of PNS
- elevated protein in CSF
- Ascending paralysis
What are the three major steps in neuron activation?
- Receive stimuli
- Integrate the input
- APs are activated at trigger zone: area with increased number of sodium channels
What is a resting membrane potential and what is it produced by?
The charge across a neuronal membrane
Most neurons: -65 mV (-40 to -90 mV)
Na+, Cl-, Ca2+ : out > in
K+ : in > out
Produced by:
- Osmotic and electrical forces
- Selective permeability
- Energy dependent Na+/K+ pump
What are 4 locations of neuron-to-neuron synapses?
AD: axodendritic
AA: axoaxonal
AS: axiomatic
DD: Dendrodendritic
Presynaptic Inhibition vs. Post-synaptic Inhibition
Presynaptic: inhibitory inputs at axon terminals (no NTM release) - collateral benefit
Post-synaptic: inhibitory inputs on post-synaptic neuron cell body may inhibit entire neuron (no collateral benefits)
Explain saltatory conduction in myelinated axons.
inc. saltatory conduction (AP jump from one node of Ranvier to the next)
inc. axon diameter inc. conduction velocity b/c of larger internodal spaces and inc. space constant
What is a tripartite synapse?
Astrocytes play imp role in at synapses - take up NTMs and excess K+ after an excitatory synaptic connection has happened
Describe the differences between IPSPs and EPSPs and the typical ion channels that produce them.
Excitatory post-synaptic potentials (EPSPs) - depolarizing postsynaptic potentials (excitatory, graded) - Na+/Ca2+
Inhibitory - hyper polarizing - Cl-/K+
