aging Flashcards
•Cognitive decline in aging humans •Aging and the Prefrontal Cortex –Deficits in working memory –Morphological changes in area 46 –Changes in electrophysiological properties of neurons •Aging and the Hippocampus –Deficits in spatial memory –No cell loss –Morphological changes •Estrogen and Aging –Effects on memory –Effects on spine morphology –Double-hit hypothesis
cognitive decline and structural changes
Cognitive decline:
- perception.
- memory encoding and retrieval
- working memory and executive functions
Structural changes:
- cortical thinning
- white matter defects
- reduction in hippocampal activation
PFC and working memory
- poor working memory in aged monkeys: delayed response and visual discrimination
- volume reduction of the dlPFC and anterior cingulate Cx
- changes in spines of layer 3 of dlPFC in rodents - 32% of spines loss on layer 3 pyramidal neurons loss with aging
compare mushroom spines and thin spines
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
DNMS acquisition in monkeys
vs synaptic density/ density of thin spines/ mean mushroom spine head volume: decrease?
vs mean thin spine head volume: increase?
age-related changes in firing of prefrontal neurons
check slide 15
hippocampus and aging - trisynaptic pathway
mossy fiber pathway
Schaffer collateral pathway
perforant fiber pathway
poorer spatial memory in aged rats
Morris water maze task
morphological changes in the hippocampus and MTL cortex
- 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?
no change in total number of hippocampal or MTL neurons in monkeys
granule cells
CA3/2, CA1
parahippocampal region
synaptic changes in the dentate gyrus
from young to aged:
SSB to NSB
MSB to SSB
MSB to MSB with less synaptic boutons
performance on the delayed nonmatching-to-sample task
slide 21
estradiol and dendritic arbor of layer 3 PFC neurons
effect of estrogen decline: estradiol vs Veh
take home message
- 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.
- The neural changes in the dlPFC occur generally earlier than those in the hippocampus.
- In both areas, age-related cognitive decline is more likely to be associated with alterations in synaptic connectivity than with neuronal loss.
changes in dlPFC
- No cell loss, but:
- Decrease in dlPFC volume due to:
- Decline in density of synapses
- Loss of neuropil but not all synapses - Mostly axospinous synapses are affected in Layer 3 and 5, but only changes in Layer 3 correlate with working memory loss.
- Extensive loss of myelinated fibers and presence of myelin defects
- Increased excitability of layer 2/3, but not layer 5
changes in the hippocampus and MTL cortex
- 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?
- Adverse effects of estrogen decline on aging processes in women.