# CHOLINERGIC CIRCUITS AND HIPPOCAMPAL FUNCTION IN AGING

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 1992 · $66,100

## Abstract

Severe deterioration in the ability to learn and remember is a hallmark of
patients with Alzheimer's disease.  Foremost among the neuropathological
changes that occur in the brains of the victims of Alzheimer's disease is a
loss of basal forebrain cholinergic neurons.  The loss of cholinergic
innervation to the hippocampal formation, a brain region known to be
necessary for the formation of new long-term memories, is thought to be
major contributor to memory loss.  The objective of the experiments
described in this proposal is to understand the contributions of muscarinic
and nicotinic cholinergic function in the hippocampus to
hippocampus-dependent learning and memory.  A rodent model will be used to
determine the relationship between age-related alterations in cholinergic
neurotransmission in the hippocampus and the mnemonic deficits with aging.
Experimental measures of cholinergic function will be assessed in rats of
different ages after their learning ability has been evaluated using the
Morris water maze, a place learning task known to depend upon intact
cholinergic input to the hippocampus, and for which age-related decrements
have been well documented.  Subsequently, several measures of cholinergic
function will be evaluated:  1) the responsiveness of hippocampal neurons
to local application of muscarine and nicotine; 2) the capacity of
intrinsic hippocampal connections to demonstrate long-lasting synaptic
plasticity, and the ability of muscarinic and nicotinic drugs to modulate
this phenomenon; and 3) biochemical measures of the status of the
cholinergic projection to the hippocampus, including measures of choline
acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity, the
status of pre- and post-synaptic nicotinic receptors.  A key element of the
experimental design is that ages of the rats to be tested will be selected
so that the influences of aging and cholinergic system function upon
learning ability can be independently evaluated.  Thus, in addition to
using young (3 months old; learning unimpaired) and aged (24 months old;
learning impaired) rats in the experiments, a third group (20 months old)
be used.  In this latter population, some animals will have intact learning
ability, while others will be learning impaired.  Within-subject
comparisons of learning ability and measures of hippocampal cholinergic
function can be made in this group independent of age, and will provide the
strongest test of correlations between physiological/biochemical parameters
and learning ability.  Finally, the effect of chronic infusion of nerve
growth factor (NGF), a trophic substance which is necessary for the
survival of central cholinergic neurons, upon the above described
behavioral and electrophysiological/biochemical measures will be evaluated.

## Key facts

- **NIH application ID:** 3122716
- **Project number:** 5R01AG010755-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** GREGORY M ROSE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $66,100
- **Award type:** 5
- **Project period:** 1991-09-29 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122716

## Citation

> US National Institutes of Health, RePORTER application 3122716, CHOLINERGIC CIRCUITS AND HIPPOCAMPAL FUNCTION IN AGING (5R01AG010755-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122716. Licensed CC0.

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