Cognition And Memory Flashcards
1
Q
HM
A
- partially spared retrograde amnesia
- impaired anterograde amnesia
- MTL damaged (hippocampus)
- working memory in tact
- procedural memory in tact
- difficulty with episodic, declarative memory
2
Q
Redefining procedural memory pathway
A
- hippocampus is not needed to process procedural memories
- log-term procedural memories are stored in basal ganglia, cerebellum and motor cortices
3
Q
Declarative memory
A
- episodic (events)
- semantic (facts)
4
Q
Nondeclarative memory
A
- skill learning
- priming
- conditioning
5
Q
Cell assembly
A
-ensembles of neurons linked via hebbian synapses could store memory traces
6
Q
Charles Sherrington
A
- speculated that alterations in synapses were the basis for learning
- changes can be presynaptic, postsynaptic or both
- changes can include increase NT release or effectiveness of receptors
- structural changes at the synapse may provide long-term storage
- new synapses could form or Somme could be eliminated over time/training
- training/experience might lead to synaptic reorganization
7
Q
Memory storage requires neuronal remodelling
A
-lab animals living in complex environment demonstrated biochemical and anatomical brain changes from those I’m simpler environment
- 3 conditions
1. Standard condition
2. Impoverished condition
3. Enriched condition - animals in EC developed thicker cortex
- enhanced cholinergic activity
- more dendritic branches (esp on basal dendrites)
- more spines suggesting more synapses
8
Q
Storing information in NS
A
- hebbian synapses occur when successful stimulation of a cell by an axon leads to enhanced ability to stimulate that cell in the future
- increases in effectiveness occur because of simultaneous activity in the presynaptic and postsynaptic neurons
- such synapses may be critical for many kinds of associative learning
-aplysia (invertebrate) studied due to large neurons
9
Q
Habituation
A
-decrease in response to a stimulus that is repeatedly presented an accompanied by no change in other stimuli
- results in a change in the synapse between sensory neurons and motor neurons
- sensory neurons fail to excite motor neurons as they did previously
10
Q
Sensitization
A
-an increase in response to a mild stimulus as a result to previous exposure to a more intense stimulus
- changes at the synapse include:
- serotonin release from a facilitating neurons blocks K+ channels in presynaptic neuron
- prolonged release of transmitter from that neuron results in prolonged sensitization
11
Q
Aplysia
A
-used to study plastic synaptic changes in neural circuits
- has fewer nerve cells
- can create detailed circuit maps for particular behaviours
- shows habituation
- squirts of water in siphon cause it to retract gills
- habituation causes it to retract less
- habituation caused by synaptic changes between sensory cell in siphon and motor neuron that retract gill
- less NT release in synapse results in less retraction
- over several days, habituated faster
- represents long term habituation
- number of synapses between sensory cell and motor neuron is reduced
12
Q
LTP
A
- first described by Bliss and Lomo (1973) at glutamatergic synapses in hippocampal formation
- dorsal hippocampus of anaesthetized rabbit was exposed
- high frequency stimulation of performance pathways fibres (inputs) to dentate gyrus cells produces an increase in amplitude of excitatory postsynaptic potentials
- lasting for hours or days
- high frequency stimulation cause LTP
13
Q
Facilitation
A
-amplitude of postsynaptic response increases when postsynaptic cell is activated several time in quick succession
14
Q
Tetanus
A
-brief increase of electrical stimulation that triggers thousands of axon potentials
15
Q
LTP
A
-stable and enduring increase in effectiveness of synapses
16
Q
LTP in hippocampus
A
- tetanus drives repeated firing
- postsynaptic targets fire repeatedly due to stimulation
- synapses stronger than before
17
Q
Storing info in NS
A
-LTP occurs when one or more axons bombard a dendrite with stimulation
- properties of LTP that suggest learning and memory
1. Specificity- only synapses onto a cell that have been highly active become strengthened
- Co-operativity
- simultaneous stimulation produces LTP much more strongly than one stimulation by single axon
- Associativity
- pairing a weal input with a strong input enhances later responses to weak input
18
Q
Synaptic plasticity in hippocampus
A
- LTP in hippocampal formation (hippocampus, dentate gyrus and subiculum)
- hippocampus has CA1, CA2, CA3
19
Q
LTD
A
- long term depression
- prolonged decrease in response at a synapse that occurs whe axons have been active at a low frequency
20
Q
AMPA receptors
A
-bind glutamate agonist AMPA
21
Q
NMDA receptors
A
-names after selective ligand NMDA
22
Q
Neurochemical changes of LTP in CA1 region
A
- transcription dependent
- Actinomycin D inhibited maintenance of LTP in rats
- Actinomycin D inhibits transcription by binding DNA
- glutamate activates AMPA-R
- NMDA receptors dont response UNTIL enough AMPA-R are stimulated and neuron is partially depolarized (-35mV)
- NMDA-R at rest have Mg2+ block on Ca2+ channels
- repeated glutamate excitation of AMPA depolarizes membrane and Mg2+ block removed from NMDA
- Ca2+ can enter NMDA and activate protein kinases
- CaMKII causes more AMP-R to be produced
- moves existing AMPA into active synapse
- increase conductance of Na+ and K+ ions
-dendritic branching increased
23
Q
Neurochemical changes cont
A
- strong stimulation of POSTSYNAPTIC cells releases retrograde messenger (CO or NO) that travels across synapse and alters function of presynaptic neuron
- decreases AP threshold
- increase release of NTs
- expansion of axons
- NT release from additional sites
-these increase sensitivity to glutamate to strengthen synapse
24
Q
CREB
A
- activation of protein kinases also triggers protein synthesis
- CREB (cAMP responsive element biding protein) activated
- CREB binds to cAMP in DNA promoter region
- CREB changes the transcription rate of genes
- regulated genes then produce proteins that affect synaptic function and contribute to LTP (eg more AMPA and NMDA receptors)
25
LTP as a part of learning and memory formation
1. correlational
- time course of LTP similar to that of memory formation
2. Somatic intervention exp.
- pharmacological treatments that block LTP impair learning
3. Behavioural intervention exp.
- training an animal in a memory task induces LTP
26
HDAC inhibitors
- TSA and sodium butyrate both enhance induction of LTP
| - inhibit acetylation
27
Contextual fear conditioning behaviour paradigm
- animal in training chamber paired foot shock to light of being removed from box
- contextual fear memories are stored within amygdala and area CA1 of hippocampus for at least 24. Hr after contextual fear conditioning
28
HDAC inhibitors
- increased histone h3-acetylation and enhanced the formation of long term contextual fear memory
- enhance freezing behaviour
-HDACI (SB) did not effect animals ability to perceive and respond to foot shock
29
DNMT inhibitor in hippocampus
-blocks formation of LTP
- animals injected with DNMT-I (sits in replication fork to stop methylation)
- did not effect animals ability to perceive and respond to foot shock
-DNMT-I specifically blocked formation of long-term contextual fear memory
- injected with HDACI and then DNMT-I DO NOT show memory impairment
- due to timing
- treating with TSA opens chromatin and allow demethylation machinery to come in, then no DNMTs present to Change activity
- demethylation has already occurred
30
Histone acetylation in LTP
-DNMT activity not only necessary for memory and plasticity but that DNA methylation works in concert with histone modifications to regulate plasticity and memory formation in hippocampus
- particular methylation patterns are important
- DNMT inhibitor strips off all methylation
31
Events
- activation of AMPA
- removal of Mg2+ from NMDA
- influx Calcium
- activate PKC
- extracellular kinase
- phosphorylation of CREB
- recruitment of CBP
- acetylation
32
Molecular basis of aging-related memory decline
-decrease in spatial memory and navigational skills
- causes:
- impairment of coding and retrieval -less cortical activation in some tasks
- loss of neurons and connection
- deterioration of cholinergic pathways (provide input to hippocampus and cortex)
- Ach pathways lost in Alzheimer’s
- enhancing cholinergic transmission helps with memory tasks
33
Improving cognitive functions
- Nootropics
- enhance cognitive function
- AChE inhibitors
- AMPAkines (bind AMPA-R and enhance hippocampal LTP) increase calcium
- PKMZ needed for LTP and memory traces (retardation if impaired)
- lifestyle factors
- living in favourable environment (less glucocorticoid)
- stimulating activities
- having partner of high cognitive status
- epigeneotype shaped by lifestyle
- epigenetic mechanisms (ncRNA) involved in memory formation
- diet and housing
- aging associated with disruption of memory-triggered epigenetic changes
- development of selective memory enhancing drugs
- opposite: PTSD drugs to help
34
Nootropic effects and benefits
- yerkes-Dodson’s law
- certain stimulants enhances cognition non low doses but at high doses results in cognitive deficits
- difficult task
- multiple pathways may be involved and if the drug only targets one pathway it may impair function overall
- need selected paths working in coordinated fashion
-AMPA and NMDA have glucocorticoid receptors
