NEUROBEHAVIORAL RELATIONS IN SENESCENT HIPPOCAMPUS

Project: Research project

Project Details

Description

This research program is directed towards an understanding of the
neurophysiological, neurochemical, and behavioral correlates of the decline
in spatial cognition with age, and the development of preventative and/or
ameliorative treatments for this decline. The investigations focus on
aging of the rodent hippocampal system, and its major cortical and
subcortical connections. Aged animals are deficient in the retention of
long-term enhancement of hippocampal synaptic transmission (which is
currently a strong candidate mechanism for associative memory storage);
furthermore, there is a break down, with age, in the specificity and
reliability of spatial information processsing by single neurons in the
aged hippocampus. The proposed experiments will continue the study of the
mechanisms of age-changes in synaptic modifiability and their relation to
memory decline and will investigate possible means of altering this decline. In order to gain a more complete understanding of the neurobiological basis
of spatial cognitive changes with age, a detailed study is proposed of the
neurophysiology and neuropharmacology of other major afferent and efferent
systems of the hippocampus, beginning, in the present proposal period, with
the cholinergic septo-hippocampal projection. This projection is strongly
implicated both in spatial memory and in the regulation of information
processing in the hippocampal formation leading to place specificity in the
discharge pattern of its single neurons. Three approaches will be taken to
this problem: 1) investigation, by means of electrically evoked field
potentials in conscious animals, of changes in septal facilitation of
hippocampal postsynaptic excitability and the modulation by this pathway of
synaptic enhancement; 2) neuropharmacological analyses of changes in
postsynaptic responsiveness (recorded both extracellularly and
intracellularly) of nicotinic and muscarinic cholinergic agents applied by
microiontophoretic methods both in vivo and in vitro; 3) examination of age
influences on spontaneous unit activity and local circuit interactions in
medial septal nucleus during performance of behavioral tasks designed for
the analysis of spatial cognition, using a technique for simultaneous
recording of multiple single units in behaving animals recently developed
in this laboratory.
StatusActive
Effective start/end date5/1/8211/30/20

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $764,386.00
  • National Institutes of Health: $383,121.00
  • National Institutes of Health: $636,387.00
  • National Institutes of Health: $674,563.00
  • National Institutes of Health
  • National Institutes of Health: $227,574.00
  • National Institutes of Health: $160,290.00
  • National Institutes of Health: $197,592.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $264,786.00
  • National Institutes of Health: $815,314.00
  • National Institutes of Health: $735,153.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $760,616.00
  • National Institutes of Health
  • National Institutes of Health: $674,882.00
  • National Institutes of Health
  • National Institutes of Health: $272,670.00
  • National Institutes of Health
  • National Institutes of Health: $649,624.00
  • National Institutes of Health: $257,124.00
  • National Institutes of Health: $637,763.00
  • National Institutes of Health
  • National Institutes of Health: $645,920.00
  • National Institutes of Health
  • National Institutes of Health: $648,355.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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