NEUR 0010 - Chapter 25 Flashcards
What is nonassociative learning?
The change in behavioral response over time to a single type of stimulus
What are the two types of nonassociative learning?
Habituation and sensitization
What is associative learning?
When you form associations between two events
What are the two types of associative learning?
Classical and operant conditioning
What is classical conditioning?
Associating a stimulus that evokes a measurable response with a second stimulus that normally doesn’t evoke that response; using a US paired with a CS to evoke a CR
What is instrumental conditioning? (Operant)
Associating a response (motor act) with a meaningful stimulus (reward)
Based on the sea slug gill withdrawal reflex, where does habituation occur?
In the synapse between the sensory neuron and the motor neurons
What did Kandel discover about the nature of habituation in the sensorimotor synapse?
That it’s caused by fewer quanta of synaptic vesicles released per AP, and thus is a presynaptic modificationi
Based on the sea slug gill withdrawal reflex, how does sensitization occur?
Shock to the head synapses onto the sensory neuron’s axon terminal; releases serotonin to make more Ca2+ enter the sensory axon terminal by using cAMP/PKA to close K+ channels and allow more Ca2+ to have prolonged entry: causes more quanta of NT to be released
What property of adenylyl cyclase makes it a good detector of CS-US coincidence?
It makes more cAMP in the presence of elevated Ca2+ concentration
How does adenylyl cyclase contribute to associative learning?
Sensory axon terminal: allows in Ca2+ after the AP from the CS, influx of 5HT from the shocked neuron activates adenylyl cyclase from the US; since adenylyl cyclase increases with Ca2+, more cAMP and PKA are produced when the US is paired with the CS: causes more K+ channels to close, prolonged Ca2+ elevation, prolonged EPSP, and more quanta of NT released
According to the sea slug associative learning hypothesis, what is learning vs memory?
Learning is when the CS causes elevated Ca2+ in coincidence with activated adenylyl cyclase from the US; Memory is when the K+ channels and closed and the NT release is enhanced
What are the two layers of the cerebellar cortex?
Purkinje cell layer; granule cell layer
What are Purkinje cells?
In the cerebellar cortex: dendrites only extend to the molecular layer; synapse on neurons in deep cerebellar nuclei (major output of cerebellum); use GABA as NT (inhibitory)
What are the two sources of input to the cerebellar cortex?
Climbing fibers (from the inferior olive in the medulla) and Mossy fibers (from the pontine nuclei in the cerebral neocortex)
What are climbing fibers?
From inferior olive to Purkinje cells: makes hundreds of large EPSPs that always activate Purkinje cell;
What are mossy fibers?
From pontine nuclei to cerebellar granule cells: relay info from the cerebral neocortex
What are cerebellar granule cells?
Small, packed, numerous: give rise to parallel fiber axons that run along the Purkinje cell dendrite plane in the top layer of cerebellar cortex
How many inferior olive climbing fibers contact each Purkinje fiber?
One climbing per Purkinje
How many cerebellar granule parallel fibers contact each Purkinje fiber?
Many, but each parallel fiber touches the same Purkinje only once and briefly
What is the Marr-Albus theory of motor learning?
Predicts plasticity of parallel fiber synapse if it is active at the same time as the climbing fiber input to the postsynaptic Purkinje cell
What is long term depression in the parallel fiber synapses?
When pairing stimulation of the parallel fibers and climbing fibers, activation of the parallel fibers alone will cause a smaller postsynaptic response in the Purkinje cell; occurs ONLY in parallel fiber synapses that are active at the same time as climbing fibers (input specificity)
What are the two major differences in sea slug associative learning and cerebellar LTD?
Slug = change occurs at presynaptic terminal, increases response; Cerebellum: change occurs at Purkinje dendrite, decreases response
Where is the parallel fiber-Purkinje synapse modified? How?
Postsynaptic: on the Purkinje dendrite; decreased postsyn response to glutamate from the parallel fibers; glutamate receptor that mediated EPSP si AMPA: internalized by the postsyn cell following LTD induction, so the synapse is less sensitive to glutamate
What kind of glutamate receptor is responsible for the LTD in parallel fiber-Purkinje synapses?
AMPA receptors: internalized following LTD induction, making the Purkinje less sensitive to glutamate and decreasing the response
What happens, molecularly, when the climbing fiber sends an AP to the Purkinje cell?
Very strong EPSP: opens up the Na+ channels to conduct an AP, BUT ALSO opens Ca2+ channels
What happens, molecularly, when the parallel fiber synapses on the Purkinje cell?
Parallel fiber releases glutamate, to reach the AMPA receptors on the Purkinje cell membrane (these allow Na+ in after the climbing fiber conducts an EPSP), but another glutamate receptor (metabotropic) couples with G-protein and PLC to create PKC
What three molecular events converge to cause LTD?
Increased Purkinje dendrite [Ca2+] from the climbing fiber; Increased [Na+] due to AMPA receptor activation from glutamate release by the parallel fiber; Increased PKC created by the G-protein/PLC cascade from the metabotropic glutamate receptors on the Purkinje dendrite membrane
What do increased [Na+], increased [Ca2+], and increased PLC do to cause LTD in cerebellar cortex?
Cause a decrease in AMPA receptors: make the Purkinje cell dendrite less receptive to glutamate
What are the two sheets of the hippocampus?
Dentate gyrus and Ammon’s horn
What is the dentate gyrus?
One of the sheets of the hippocampus
What is Ammon’s horn?
One of the sheets of the hippocampus; has four divisions, CA1-4
What is one of the major inputs to the hippocampus?
Entorhinal cortex
By what path does the entorhinal cortex input to the hippocampus?
The perforant path
What is the perforant path?
Input from the entorhinal cortex to the hippocampus: its axons synapse on the neurons of the dentate gyrus, which sends mossy fiber axons to CA3 in Ammon’s horn, which branch and send axons to the fornix and CA1 (Schaffer collateral)
Describe the steps of the perforant path.
Entorhinal cortex sends axons to the dentate gyrus, which send mossy fiber axons to CA3 in Ammon’s horn, which sends axons to the fornix and sends the Schaffer collateral axons to CA1
What are the properties of LTP in CA1?
Caused by tetanus (rapid frequency APs) to presynaptic Schaffer collateral axons; causes a greater EPSP than expected; lasts for weeks to a lifetime; doesn’t require high-frequency APs (but does require that the synapse is active at the same time as the postsynaptic CA1 neuron is strongly depolarized)
What two conditions are necessary for an LTP to occur in a Schaffer collateral presynaptic axon - CA1 synapse?
1) synapses must be stimulated at frequency high enough to cause temporal summation of EPSPs, and 2) enough synapses must be stimulated together to cause spatial summation (cooperativity)
What two things must occur simultaneously for an LTP to occur between Schaffer collateral axon and CA1?
Synapse must be active at the SAME time that the postsynaptic CA1 neuron is strongly depolarized
What neuroscience saying is indicative of the creation of LTPs between Schaffer collateral axons and CA1?
Fire together, wire together!
How does EPSP transmission differ in the CA1 pyramidal cells from the cerebellar cortex cells?
In addition to containing AMPA receptors, also contain NMDA receptors
Why is it significant that CA1 pyramidal cells contain both AMPA and NMDA glutamate receptors?
NMDA receptors conduct Ca2+ IFF glutamate binds and the postsynaptic membrane is depolarized enough to displace the magnesium block: WHICH MEANS: only allows Ca2+ through when the presynaptic and postsynaptic elements are active simultaneously
What does the rise in [Ca2+] in the postsynaptic element during EPSP transduction using NMDA receptors create?
PKC and CaMKII (calmodulin dependent protein kinase II)
What is the BCM theory?
Accounts for the bidirectional regulation of synaptic strength; synapses that are active when the postsynaptic cell is weakly depolarized undergoes LTD instead of LTP
How does [Ca2+] influx cause both LTP and LTD?
Level of NMDA activation and Ca2+ influx: if the cell is weakly depolarized, the Mg2+ block isn’t moved from the NMDA receptors, so only a little Ca2+ in (causes LTD); if cell highly depolarized, Mg2+ block completed moved, and Ca2+ floods in (causes LTP)
What opposing actions for Ca2+ cause to create LTD vs LTP?
Low Ca2+ activates protein phosphatases to cause dephosphorylation (LTD), whereas high Ca2+ activates PKC and CaMKII to phosphorylate (LTP)
What is the molecular switch hypothesis?
The idea that an autophosphorylating kinase can store info at the synapse by keeping its “pocket knife” configuration open
When is new protein synthesis most critical for LTM formation?
During the consolidation period after training
What is CREB?
A protein transcription factor: cAMP response element binding protein
What does CREB do?
Binds to specific DNA segments (cyclic AMP response elements, or CREs) and regulates the expression of neighboring genes
What are the two different forms of CREB, and what does each do?
CREB-2 (represses gene expression when bound to the CRE) and CRED-1 (activates transcription IFF phosphorylated by PKA)
