aging

Question 1

cognitive decline and structural changes

Answer 1

Cognitive decline:

• perception.
• memory encoding and retrieval
• working memory and executive functions

Structural changes:

• cortical thinning
• white matter defects
• reduction in hippocampal activation

Question 2

PFC and working memory

Answer 2

1. poor working memory in aged monkeys: delayed response and visual discrimination
2. volume reduction of the dlPFC and anterior cingulate Cx
3. changes in spines of layer 3 of dlPFC in rodents - 32% of spines loss on layer 3 pyramidal neurons loss with aging

Question 3

compare mushroom spines and thin spines

Answer 3

Mushroom spines:

• High degree of stability
• Mediate strong synaptic currents via AMPA receptors

Thin spines:

• Less stable, i.e. can be stabilized or retract
• High degree of plasticity

Question 4

DNMS acquisition in monkeys

Answer 4

vs synaptic density/ density of thin spines/ mean mushroom spine head volume: decrease?

vs mean thin spine head volume: increase?

Question 5

age-related changes in firing of prefrontal neurons

Answer 5

check slide 15

Question 6

hippocampus and aging - trisynaptic pathway

Answer 6

mossy fiber pathway
Schaffer collateral pathway
perforant fiber pathway

Question 7

poorer spatial memory in aged rats

Answer 7

Morris water maze task

Question 8

morphological changes in the hippocampus and MTL cortex

Answer 8

• No cell loss in H and MTL
• Alterations in synapses
• Reduction in synaptic contacts per axonal bouton
• Increase in non-synaptic boutons in the portion of the molecular layer that receives input from the entorhinal cortex
• Decline in neurogenesis in the DG?

Question 9

no change in total number of hippocampal or MTL neurons in monkeys

Answer 9

granule cells
CA3/2, CA1
parahippocampal region

Question 10

synaptic changes in the dentate gyrus

Answer 10

from young to aged:
SSB to NSB
MSB to SSB
MSB to MSB with less synaptic boutons

Question 11

performance on the delayed nonmatching-to-sample task

Answer 11

slide 21

Question 12

estradiol and dendritic arbor of layer 3 PFC neurons

Answer 12

effect of estrogen decline: estradiol vs Veh

Question 13

take home message

Answer 13

1. The cognitive processes that are mediated by the dorsolateral prefrontal cortex (dlPFC) (for example, working memory or source memory) and the hippocampus (for example, declarative memory) are the most vulnerable to aging.
2. The neural changes in the dlPFC occur generally earlier than those in the hippocampus.
3. In both areas, age-related cognitive decline is more likely to be associated with alterations in synaptic connectivity than with neuronal loss.

Question 14

changes in dlPFC

Answer 14

1. No cell loss, but:
2. Decrease in dlPFC volume due to:
   - Decline in density of synapses
   - Loss of neuropil but not all synapses
3. Mostly axospinous synapses are affected in Layer 3 and 5, but only changes in Layer 3 correlate with working memory loss.
4. Extensive loss of myelinated fibers and presence of myelin defects
5. Increased excitability of layer 2/3, but not layer 5

Question 15

changes in the hippocampus and MTL cortex

Answer 15

1. No cell loss in H and MTL
2. Alterations in synapses:
   - Reduction in synaptic contacts per axonal bouton
   - Increase in non-synaptic boutons in the portion of the molecular layer that receives input from the entorhinal cortex
3. Decline in neurogenesis in the DG?
4. Adverse effects of estrogen decline on aging processes in women.