# AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

> **NIH NIH RF1** · RUTGERS THE STATE UNIV OF NJ NEWARK · 2020 · $2,889,562

## Abstract

The broad objective of this research program is to understand how the basal forebrain (BF) cholinergic system
(BFC) contributes to specific cognitive operations in anatomically defined circuits. Despite its involvement in
cortical activation, attention, and memory, the functional details of the BF are not well understood due to the
anatomical complexity of the region. Patients with Alzheimer's disease and related dementias have a significant
decrease of acetylcholine (ACh) in the cortex and show pathological changes in cholinergic neurons in the BF.
Thus, a complete understanding of its functional organization is warranted. The central hypothesis of our long-
standing anatomical studies is that cholinergic projections to the neocortex are not diffuse, but instead are
organized into segregated or overlapping pools of projection neurons. While our earlier model dealt with high
density projection volumes only, which represent only about 16-30% of cholinergic projection neurons, we now
parcel the whole cholinergic space by classifying local projection patterns. According to these studies, cholinergic
cells are segregated into topographical sets of clusters projecting to functionally connected cortical targets. In
Specific Aim 1 in various BF locations in ChAT::Cre rats, we will apply systematic small injections of AAV coding
for the inhibitory DREADD in order to inhibit of the cholinergic projection group within subregions of BF. We will
investigate spatio-temporal EEG changes in response to BF cholinergic inhibiton over large parts of the cortex
in order to lend support to our idea that the clusters modulate functionally related cortical regions. In Specific
Aim 2 using high-density silicon arrays in the orbitofrontal, visual association cortex and the basal forebrain in
ChAT::Cre rats during a touchscreen-based visual discrimination task, we will investigate the dynamic pattern of
neural activity with millisecond precision to understand cholinergic-related modulatory changes within an
anatomically defined neuronal network during specific behavioral epochs, including cue detection, short-term
memory, decision making, and behavioral execution. Finally, in Specific Aim 3 we will investigate how activity
changes over time in the striatal GABAergic-cholinergic–auditory cortical circuits, during an auditory operant
conditioning task, in order to understand how changes between cortical map plasticity and electrophysiological
profiles of specific striatal and cholinergic neurons relate to cholinergic-dependent auditory plasticity, learning,
memory, and cognitive flexibility. The study of the functional organization of the basalo-cortical network and
distinct functions of the cholinergic signal at cellular, network and behavior levels will contribute to better
understanding of the dysfunction of attention, decision-making, and memory processes, central to the symptoms
of Alzheimer's and other forms of cognitive decline.

## Key facts

- **NIH application ID:** 9889668
- **Project number:** 2RF1NS023945-28
- **Recipient organization:** RUTGERS THE STATE UNIV OF NJ NEWARK
- **Principal Investigator:** LASZLO ZABORSZKY
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,889,562
- **Award type:** 2
- **Project period:** 1986-08-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889668

## Citation

> US National Institutes of Health, RePORTER application 9889668, AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS (2RF1NS023945-28). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9889668. Licensed CC0.

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