Neur 202 Exam 2

working memory

~ 10 seconds, neural activity outlasts the stimulus. holds up to 7 items in memory. Example: remembering a phone number long enough to dial it

short-term memory

minutes to hours; requires consolidation to be permanent

consolidation and its pathway

The process of stabilizing a memory trace after initial encoding, making it a long-term memory. sensory —> short term —> long term

three lines of evidence for consolidation

1) head trauma and electro-convulsive shock disrupt recent memory more than older ones

2) can’t consolidate new long-term declarative memory without the hippocampus (patient HM)

3) new protein synthesis is required to hold memory for longer than a few hours

learning

acquisition of altered behavioral response due to environmental stimulus

memory

processes thorugh which the learned response is stored

recall

conscious or unconscious retrieval process through which this altered behavior is manifested

What kind of memory is encoded in the striatum?

motor skills and habits, procedural memory, non-declarative memory

long-term memory

due to physical changes in neurons, especially at the synapse; can store many memories

What kind of memory is encoded by the hippocampus and medial temporal lobe?

declarative memory

Describe double disassociation experiments

The double-dissociation between declarative and procedural memory shows that the striatum is involved in non-declarative memory and not declarative memory, and the medial temporal lobe and hippocampus are involved in declarative memory and not non-declarative memory. This shows that these two brain areas have distinct and non-overlapping roles in encoding types of memory.

 

Specifically, researchers conducted two separate tasks that tested declarative and non-declarative memory in individuals with Parkinson’s (which affects the striatum), amnesia (which affects the hippocampus), and controls.

In the declarative task (a questionnaire), [CL1] Parkinson’s patients and control individuals performed better. This shows that striatum damage does not affect declarative memory. In contrast, amnesia patients performed worse on this task, showing that the hippocampus and medial temporal lobe are involved in encoding declarative memory.

For the non-declarative task, researchers conducted a “weather predict” task[CL2]  with cards. Participants were asked to guess which cards predicted what weather. Control and amnesia patients performed better in this task, showing the medial temporal lobe and hippocampus do not affect non-declarative memory. Parkinson’s patients performed worse on this task, showing that the striatum is involved in encoding non-declarative memory.

 

Additionally, researchers also conducted a study of rats with a radial arm maze. Rats were placed at the center of the maze, with food placed at the end of each arm. In rats with hippocampal lesions, they were unable to remember which arms they had already explored, but they were able to learn where food was placed if it was consistently placed in one location. However, for rats with striatal lesions, their performance was unaffected. This shows the hippocampus is necessary for declarative learning.

In a similar task, arms in the maze that contained food were marked by a light. This tested procedural (non-declarative) memory. Rats with striatal lesions had impaired performance on this task, whereas rats with hippocampal lesions were unaffected. This shows that non-declarative memory is associated with the striatum and not with the hippocampus.

Three reasons to associate medial temporal lobe with declarative memory

1) HM could not consolidate new memories without medial temporal lobe

2) monkeys could not consolidate short-term memories in DNMS without MTL

3) electrical stimulation led to recall of complex past experiences (wilder penfield)

Hippocampus functions

• memory consolidation

• spatial memory

• working memory

HC spatial memory evidence

• hippocampal place cells - single cell firing rate code correlate with specific locations

• grid cells - active at multiple locations that form a grid pattern (in rats)

• Morris water maze - mouse looks for a hidden platform and learns its location. Can’t find location w/ HC lesion

HC working memory evidence

radial arm maze - will go to different arms; damaged HC - will go back to same arms

Hebb’s cell assembly

modifications strengthen connections; after learning partial —> full activation; distributed cell assemblies represent perception and memory; sensory and percetual areas participate in memory storage

theta rhythm occurs when/indicates state of

activity, voluntary movement, REM sleep, etc.

presynaptic mechanisms for molecular memory and increasing synaptic strength (3)

1. increase number of vesicles with neurotransmitters

2. increase number of sites they can be released from

3. increase release probability

postsynaptic mechanisms for molecular memory and increasing synaptic strength (2)

1. increased receptor sensitivity

2. increased number of receptors

last way to increase synaptic strength

increase number of synapses

early LTP is characterized by…

protein kinase activation

late LTP is characterized by…

new protein synthesis

What is the role of CaMKII?

It is a kinase that phosphorylates other proteins. It helps early-LTP effects stay even after calcium influx has passed at the post-synaptic cell. It’s structure prevents phosphatases from removing its phosphate

gene targets in L-LTP

transcription factors:

• CREB

signaling molecule

• BDNF - triggers synaptic potentiation

structural proteins

• AMPARs

• scaffolding proteins - HOMER - for gluRs in spines

• cytoskeletal proteins - Arc

limitations of pharmocological inactivation compared to genetic deletions

• drugs are promiscuous

• drug effects are less reproducible from animal to animal

• drug concentrations vary spatially

• drugs are difficult to target a specific cell type

limitations of conventional knockouts

1. gene is deleted in all cell types and can lead to developmental defects or death

2. it is hard to attribute the resulting phenotype to specific cells

3. the adult phenotype may arise indirectly from a developmental defect

fNR1 mice

NMDA is floxed by the loxP genes