memory, LTP and LDP mechanisms Flashcards
Learning
acquisition of information
Memory
storage of learned information
Recall
reacquisition of stored information
The engram
physical embodiment of a memory
Procedural memory
Skills and associations largely unavailable to conscious mind
e.g riding bike
Declarative memory
Available to conscious mind. Can be encoded in symbols and language
e.g capital of france
Explicit memory
memory that can be consciously recalled (e.g. recalling riding a shiny new bike on the Christmas day when you were 5)
Implicit memory
memory that cannot consciously recalled (e.g. learning to ride a bike). Can be different types:
- Procedural memory
- Classical conditioning
- Priming (when one stimulus influences the response to subsequent stimuli)
Priming
when one stimulus influences the response to subsequent stimuli
advantages of using lower vertebrates as models for simple systems
- neuronal size
- circuit complexity
- temperature dependence
- switches neurones on/off
- mapping tools
simple forms of memory
habituation = desensitisation
sensitisation
what is habituation
desensitisation of response to stimuli
- amplitude of response reduces if stimulus is repeated
- of eye blink reflex
- of repetitive non-harmful stimulus presentation
- of visual attention
- of emotional response
what is sensitisation
increases amplitude of response over time
what do studies of aplysia gill withdrawal reflex show?
- Touch or water jet causes gill withdrawal
- contains sensory neurones
- Habituation to repeated stimuli
- 10-15 touches at 10-20 sec interval reduces the reflex
- sensory neurone (siphon skin) → motor neurone (gill muscle)
origins of habituation
- pre-s neurone = regular amplitude of neurone firing
- post-s neurone = declining amplitude of neurone firing
⇒ origin is somewhere between pre and post synaptic neurone
what is the mechanism of habituation (desensitisation)
- caused by reduced transmitter release / depletion of readily releasable pool
- less vesicles available in active zone to be released = less aplitude
what is the readily releasable pool
what is released immediately when post-s depolarises (active zone)
what is the reserve pool
spare vesicles and NTs that require high depolarisation to be released
explain how desensitisation (habituation occurs)
when you stimulate specific neurones repeatedly, the amount of vesicles available to transmit neurotransmitters is depleted requiring higher stimulus to use reserves -> meaning there are weaker signals sent as a result
how does sensitisation occur
L29 sensitising neurone releases serotonin → activates adenylyl cyclase → cAMP → PKA → phosphorylation of ion channels including K channels -> longer depolarisation period = sensitised
habituation and sensitisaiton summed up in a sentence
Habituation: depletion of the synaptic vesicle pool
Sensitisation: serotoninergic feedback from other sensory neuron
how does associative learning occur in a simple model
when L29 has an EPSP -> other sensory neurones around can be depolarised causing increased depolarisation of nearby neurones
what do the mechanisms of sensitisation and conditioning typically involve
- Multiple intracellular signalling pathways
- Pre and post-synaptic
- Long term involves the nucleus
- requires changes to gene expression
what enzymes are involved in early stages of associative learning
- PK2
- activated by Ca
- PKa
- activated by cAMP?
- PKC
- activated by diceglycerol
- produced by G proteins/channels
what molecule activates PK2
Ca
what molecule activates PKA
cAMP
what molecule activates PKC
diglycerol
what enzymes are involved in late stages of associative learning
- MAP kinase
- travels from cytoplasm → nucleus and phosphorylates TF → gene expression
- proteins are transported to synapse
- establishes longer response
what is the concept of hebbian synapse
Coordinated activity of a presynaptic terminal and a postsynaptic neuron strengthen the synaptic connections between them
ie neurones that fire together wire together
major role of hippocampus
→ spatial memory formation
structure of hippocampus
- many layers
- input from entorhinal cortex
- dentate gyrus -> CA3 contains mossy fibres
- CA3 -> CA1 contains schaffer colaterals
- neuronal output via fornix and subiculum
what is cooperativity
Cooperativity refers to the need to stimulate multiple afferent fibers to induce LTP
what have experiments shown about LTP
- ca3-ca1 synapses are glutaminergic
- high freq stim (1000Hz) produces long lasting potentiation → increased firing rate
types of glutamate receptors
AMPAR
- opens = depolarises cell
- Na+
mGluR
- metabotropic
NMDA
- Ca2+
- v-dependent Mg2+ block
- phosphorylation
how do NMDA glutamate channels work
- Ca2+ channel
- activates kinases
- phosphorylates proteins to increase EPSP
- requires depolarisation to remove v-dependent magnesium block
how does early phase LTP work
- NMDAR mediated Ca activates calmodulin kinase II
- autophosphorylation and activation triggered by Ca
- phosphorylation enhances AMPA currents
- increased potentiaion = increased currents
what is AMPAfication
- pre-s excitatory signals causes delivery of ready-prepared AMPA receptors to the synapse, increasing EPSP
how does late stage LTP work
- long term storage requires protein synthesis
- cAMP → PKA → activates proteins and phos proteins in nucleus
- CREB binds to CRE to stimulate phosphorylation of CREB transcription
impact of LTP on memory formation
inhibiting LTP inhibits some memory formation
which mutations/drugs can affect learning
Mutations of CaMKII, NMDARs, cAMP pathway all affect aspects of learning
inputs and outputs of cerebellum
+ve inputs = mossy and climbing fibres (efferent)
-ve outputs = purkinje cells
synapses of climbing fibre
climbing fibre has multiple synapses on 1-10 purkinje cells1 climbing:1-10 purkinjes
synapses of mossy fibre
mossy fibres synapse onto 1 granule cell and contact 1000 purkinje neurones
1 mossy:1 granule(parallel):splits to contact 1000s purkinjes
do mossy or climbing fibres form stronger synapses?
climbing fibres, becuase its 1:1, not 1:1:1
what does activation of a climbing fibre do
depolarisation of purkinje cell
how to measure purkinje synapses
- recording purkinje cell response to parallel fibre = measure EPSP amplitude
- stimulate parallel fibre simultaneously = changes in synapse and decrease in amplitude of EPSP
which glut channels are involved in cerebellar LTD
- metabotropic Glutamate receptors, AMPA-R and V-gated Ca2+ channels - not NMDA
types of synapses in cerebellar long term depression
climbing:purkinje = AMPA receptors
granule/parallel:purkinje = metabotropic glutamate receptors
- stimulate only parallel fibre = not much PKC activated
- stimulate climbing + parallel = lots of AMPA activation → strong depolarisation of purkinje cell → V gated Ca2+ increased ic[Ca2+] → Ca2+ increases activity of PKC
difference between climbing and parallel fibres
Climbing fiber synapses contact spines on the primary Purkinje cell dendrite, whereas parallel fiber synapses contact spines on secondary and tertiary dendritic branches
how does long term depression occur in cerebellum?
- climbing + parallel increases PKC activity due to Ca2+
- PKC phosphorylates AMPA GluR2 subunit
- causes AMPA receptors to be endocytosed
- reduced EPSP
how does long term depression occur in cerebellum?
- climbing + parallel increases PKC activity due to Ca2+
- PKC phosphorylates AMPA GluR2 subunit
- causes AMPA receptors to be endocytosed
- reduced EPSP
can LTD can reverse an LTP?
yes via depotentiation
how does hippocampal long term depression occur
- synapses become weakened when they are active but the rest of the cell isn’t
- LTD and LTP are Ca2+ dependent
- degree of NMDS receptor activation determines probability of inducing LTP or LTD
where does hippocampal LTD occur
- occurs at CA3-CA1 neurones synapse
what enzymes are activated via LTP
kinases
what enzymes are activated via LTD
phosphatases
role of calcium in hippocampal LTD/LTP
- small increases in Ca from NMDA trigger more phosphatase action → reduces AMPAR efficacy
- large increases in Ca from NMDA activate more protein kinases → increase AMPAR efficacy
what is adaptation
form of plasticity
change of response to same stimulus
what fluorescent proteins show proton release following NT release
- sypHy
- reporter of neural activity
- fluorescent when H+ has been exocytosed
role of - iGluSnfr protein
- fluorescent reporter of glutamate
- glutamate changes conformation of protein → bright
