Neuromodulation and Plasticity Flashcards
neuromodulation
refers to mechanisms that change how info is being processed through nervous system. Modulate neurons and neural circuits. Good drug target
Two dominant mechanisms for neuromodulation
- changing intracellular Ca2+ to trigger activation of specific Ca2+ regulatory enzyme systems
- Activation of specific G-proteins that couple to the activation or inhibition of different enzyme cascades
What are the two primary ways that intracellular Ca is raised?
- NMDA receptor
- voltage gated Ca channel
What are the primary neuromodulatory systems?
- cholinergic (CNS Ach = neuromodulatory)
- catacholamines - (i.e. dopamine)
- indoleamines - (i.e. serotonin)
- neuropeptides - change state or regulate pain
What is the primary indoleamine?
serotonin
How are peptide transmitters synthesized?
into VESICLES in ER as inactive precoursers. Proteolytic cleavage within vesicle produces active peptides
Learning/memory vs. plasticity
learning = ORGANISM LEVEL changes, change in behavior, experience
plasticity = cellular/circuit change within nervous system, changes in firing in response to the same stimulus
What is the key factor involved in learning/memory and plasticity?
EXPERIENCE!
changes can be related to a pattern of preceding experiences that trigger interonal neronal mechanisms that modulate nervous system function
Two main classes of plasticity?
excitability - changes in likelihood of firing APs in response to same stimuli
synaptic - changes in the strengths of connections between neurons
plasticity temporal domains (time classifications)
short term - (msec to sec). Involves changes in gates/cellular Ca
intermediate - (seconds to hours) - involves covalent bonds, phosphorylation, proteolysis, red-ox sensitivity
long term - (hours to days) - transcription, translation, alt splicing….needs an opposing long term plasticity mechanism to revert…HARD TO REVERSE
How are neuronal connectivity patterns regulated?
genetically regulated
How are synaptic strengths and neuronal excitability modulated?
EXPERIENCE
coincidence detection
involves response to multiple factors at the same time. specific molecular mechanisms exist that can create an association between multiple factors and produce a conditional change in enuronal function
What is the classic example of coincidence detection?
NMDA receptor
What is involved in NMDA receptor in coincidence detection?
Mg2+ blocking…this means that when Mg blocking is active, NMDA receptors can only pass current when cell is depolarized.
EXTRACELLULAR MG2+ IONS BLOCK NMDA CURRENTS AT NEGATIVE POTENTIALS
