Learning and memory

Question 1

describe learning and memory

Answer 1

Learning is viewed as acquisition or encoding the information to memory.

Memory refers to a capability of virtually any animal to encode, store and retrieve information, to guide behavioral output.

Question 2

What are the major temporal categories of memory

Answer 2

• There is immediate, short term and long term memory
• Immediate memory is when you retain something for a fractions of a second
• short term memory only lasts from seconds to minutes
• long term memory lasts from days to years.

All types of memories lead to forgetting.

Question 3

Short term memory

Answer 3

Protein synthesis independent and anesthesia sensitive

Question 4

Long term memory

Answer 4

Protein synthesis dependent, and anesthesia dependent

Question 5

Breifly describe the morris water maze

Answer 5

• it is a common test when looking at learning and memory
• We have a pool which is divided into 4 quadrants and there is a plate form hidden somewhere in the quadrants.
• we take a rat and place it in the pool
• it can eventually find the platform
• in the first few trials it will take the rat a few tries but after several tries the rat will go directly to the platform.
• this is a form of spatial learning and memory and it depends on the hippocampus

Question 6

Explain the rat with hippocampal lesions and how his spatial learning and memory was effected

Answer 6

• performed hipppocamppal lesions on a rat
• first few trials are the same as the trial mice
• but even after repeated tries the rat is still not able to find the platform
• meaning the hippocampal lesions effected his spatial learning and memory

Question 7

Synapses

Answer 7

• Santiago Ramon y Cajal (1894) first suggested that learning results from changes in the strength of the synapse based on insights from his anatomical studies
• The modulation of the synaptic connectivity is a critical mechanism oof learning was incorporated into more refined. Models by Donald herb in the 1940s and 19650s

Question 8

Describe the reductionist approach

Answer 8

• Eric Kandel took the reductionist approach
• took a simple organism like an aplysia which only has 20,000 neurons while humans have trillions of neurons.
• the simplest behaviours in aplysia can be modified by learning may directly involve less than 100 central nerve cells
• he took simple behaviour and studied is basically

Question 9

Describe the gill withdrawal reflex studied in aplysia

Answer 9

• Kandel looked at the gill withdrawal reflex; where after applying stimulus the gill would withdraw to touch
• he found that he could also sensitize this response by pairing it with a tail shock
• when he gives the tail a shock and touches the area, and the tail moves since now it is sensitized.

Question 10

what is the neural circuit of the aplysia gill reflex?

Answer 10

• If you touch the siphon, it activates sensory neurons, which synapses onto motor neurons which synapse onto gill; which is the gill withdrawal reflex
• When you shock the tail you activate various interneurons; interneurons can synapse onto motor neurons and sensory neurons leading to sensitization of response
• Simple circuit allowed him to report on neurons while looking at gill withdrawal

Question 11

Mechanisms of short term memory formation in aplysia

Answer 11

1) Presynaptic PKA
2) PresynapItc Ca and CamKII
3) Presynaptic PKC
4) postsynaptic Ca and CamKII
5) recruitment of pre and post synaptic molecules to new sites

• There is a number of kinases that are bing activates like PKA and PKC
• Ca is coming into the neuron activating CaMKII
• PKA PKC and CaMKII can all phosphorylates various targets
• Leading to more NT release
• Leads to Ca coming in and activating CaMKII in postsynaptic nuron
• Can also have recruitment of additional pre and post synaptic molecules; more AMPA and NMDA are inserted and various proteins being uprgualted

Question 12

Mechanisms of Long term memory formation

Answer 12

1) NT release and short-term strengthening of syaptic connections
2) involvement of kinases and phosphotases
3) activation of nuclear transcription factors
4) activity-dependent induction of gene expression
5) chromatin alternation and epigenetic changes in gene expression
6) synaptic growth and the formation of new synapses
7) activation of pre-existing silent synpases.

Get increase in cAMP which activates PKA, leads to various effects on kinases and phosphotases which can lead to the activation of various transcription factors in the nucleus which can then lead to changes in gene expression

Question 13

Mechanisms of LTP in the hippocampus

Answer 13

(looking at hippocampus)
* Applying short high frequency trains and looking at what effect it has on synaptic strengthning
* can see they can induce a few diff fforms of LTP in early LTP and late LTP

(looking at it mechanistically)
* In post synaptic neruons Ca coming in and activating Ca binding proteins Calmodulin
* We also see cAMP being produced by adenyl cyclase
* CAMP activates PKA
* Leading it a number of kinases which are phosphorlating various transcription factors and activating various transcription factors
* Leads to changes in gene expression

• Similar mechanisms of learning and memory in aplysia and LTP in mammalian cells

CAMP is importnt for LTP it activates PKA leads increased phosphorylation of trancription factrs which leads to changes in gene expression which can affect genes that can regulate synaptic growth, synapse formation and can also regulate synaptic strength

• There are some differences between early phase and late phase of LTP
• Late LTP requires PKA and protein synthesis
  ○ Long term memory is protein synthesis dependent while short term is Protein synthesis independent
• Looking at LTD; it can also have late and early phases of LTD
  ○ Lte phase LTD requires protein synthesis

Question 14

Mechanisms of LTP in the hippocampus (mice example)

Answer 14

Looking at learning and memory in mice
* Doing contextual conditioning; Putting a mouse in a chamber
* Then there will be a sound paired with a shock
* The idea is if you train a mouse like this, when u put the mouse back in the same context it will freeze, remembering the previous context that was paired with electrical shock
* Used as a way to test for memory in mice

Looking at wild type
* There is some immediate learning; some freezing happens when they are put back in
* When you test after an hour there is memory and if you test after 24 hrs there is some memory Again
* Used as a way to test for memory in mice

Looking at a PKA mutant
* PKA is disrupted here
* Did the same experiment but PKA was disrupted
* Found that immediate learning and memory was fine
* After one hour was it was also fine; simialr to wildtype/control mouse
* But after 24 hrs it showed significantly decrease in memory
* PKA required for long term mememory in mice

PKA required for LTP and Long term memory

B2
* Fed the mice anisomycin, which is a protein synthesis inhibitor
* Did the same assay
* Found that the wt mice that were given same; there was a certain amount of immediate learning and there was some memory after 1 hours and long term memory after 24 hrs
* In the mice that were fed protein synthesis inhibitor they found immediate memory and learning after an hour was the same
* But there was an impairment of memory after 24 hours

Long term memory requires PKA and protein synthesis

Question 15

Molecular mechanisms for induction of LTP and memory

Answer 15

• short term: we can get Ca coming into the post synaptic neuron, CaMKII and PKC get activated, leads to changes in the number of receptors found on the post synaptic neuron and more AMPA receptors will be inserted.
• Long term: we get PKA that is phosphorylating various trancription factors like CREB leading to changes in gene expression

With late LTP the activation of various transcription factors lead to changes in gene expression and eventually protein synthesis

Question 16

A number of commonalities that have been established across multiple species

Answer 16

1) synaptic change is elicited by patterns of neuronal activity at critical points within a a behavioural circuit

2) both increases and decrease in synaptic strength can contribute to behavioural plasticity

3) synaptic plasticity has similar temporal and molecular properties to behavioural learning eg short and long term phases dependent on discrete signalling pathways

4) apparently diff forms of learning use similar underlying cellular and molecular mechanisms.

Question 17

Silent synapses

Answer 17

• defined as structural specialization for neurotransmssion that do not produceA Physiological response in the receiving cell; may occur frequently in neural cirrcuits
• silent synapses maybe be importnat for several forms of synaptic plasticity and possible learning and memory And circuit modification.

Question 18

What are the diff forms of silent synapses?

Answer 18

A) functional synapse: has various pre and post synaptic components which includes AMPA and NMDA receptors

B) presynaptically silent synapse: is missing something in the Presynaptic side; some proteins is not present or it is not in the right spot. Leads to the synapse being synaptic ally silent.

C) Conditionally silent synapse: presynaptically we have all the components, and on the postsynaptic side we have NMDA receptors but no AMPA receptors. AMPA receptors are required to depolarize the neuron in order to remove the Mg block.

D) postsynaptically silent synapses: Doenst NMDA or AMPA receptors on the post synaptic side

E) Incompletely assembled synapse: On the post synaptic side, missing receptors, anchoring proteins, cytoskeletal elements.

Some of these silent synapses become active synpases

Question 19

Adult neurogenesis

Answer 19

• Neurogenesis is the process if generating functional neurons from precursors
• neurogenesis traditionally viewed to occur only during embryonic and perinatal stages in animals
• Adult neurogenesis is spatially restricted to two specific brain regions. The subgranular zone (SGZ) in the dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles where new neurons are generated and migrate through the rostrum migratory stream to the olfactory bulb to becomes interneurons.urogenesis is the process if generating functional neurons from precursors

Question 20

There is an increase in neurogenesis in the dentate gyrus of the hipppocampus of the mice that are _______ , ___________ ___________ ____________ and __________

Answer 20

Run, live in enriched environments, and excercise

Question 21

LTP enhances proliferations and survival of newborn neurons

Answer 21

• Link between neurogenic and LTP and neurognesis and the survival of new neurosn
• Inducing LTP; results in strengthening of synapses
• Looking at the number of new neurons; found In the conditions where they induce LTP there is a increase in adult neurogeneiss
• After several days if we check the survival of the neurons it increases (bc of LTP)
• More new neurons show up on the side of the brain where they induce LTP
• LTP increases adult neurogenesis

Question 22

Low does of irrigation blocks adult neurogenesis and impairs spatial memory

Answer 22

Linking adult neurogenic to learning and memeroy
* Used low levels of radiation to block adult neurongenesis
* Looked at what affects it has on spatial memory using water maze
* Found a total reduction in the number of new neurons since it is being blocked by radiation

• If you give rats low doses of radiation we block adult neurogensis and I results in imapairmnt of spatial memory when it comes to the morris water maze

Question 23

When we have increased _________ we have higher syanptic __________

Answer 23

Neurogenesis, plasticity

Question 24

Epigenetics

Answer 24

• Epigenetics refers to a set of regulatory modifications that influence gene expression above the level of the genome itself, that is, without changes in DNA sequence.
• Changes to the epigenome are a key mechanism by which cells initiate, maintain, and terminate gene expression programs, making them potent modulators of cell function and activity.
• Accumulating evidence has revealed that these mechanisms are critical components of ongoing physiology and function in the adult nervous system, and are essential for many cognitive processes, including learning and memory.
• Moreover, a number of psychiatric disorders and syndromes that involve cognitive impairments are associated with altered epigenetic function.

Question 25

Epigenitics

Answer 25

• Epigenetic mechanisms are key regulators of DNA compaction and transcription.
• DNA methylation preferentially occurs on cytosines positioned adjacent to guanine nucleobases (CpG) and is established via DNA methyltransferase (DNMT) enzymes.
• Post-translational modifications of histones are another critically important regulator of chromatin compaction and gene expression. Histones can undergo a number of modifications, including acetylation, phosphorylation, and methylation.

Question 26

Histone modification

Answer 26

• Heterochromatin is characterized by condensed chromatin and subsequent transcriptional repression.
• Euchromatin is characterized by a relaxed chromatin state that allows transcriptional machinery access to DNA for gene expression.

Question 27

What are some post—translational modifications of Histones

Answer 27

• heterochromatin represses transcription-> increase in histone methylation—> various transcription factors have less access to to the DNA itself
• euchromatin—> not a lot of methylation and there is phosphorylation/acetylation—> DNA factors have more access to DNA