# Synaptic mechanisms of auditory memory

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2021 · $460,489

## Abstract

Abstract: Primary sensory cortices analyze sensory information and store information about learned sensory
experiences. The auditory cortex (ACx) acquires and retains memory traces about the behavioral significance
of selected sounds. During learning, the tuning properties of ACx neurons undergo activity-dependent
changes. This cortical map plasticity, which is believed to be a substrate of auditory memory, is characterized
by the facilitation of responses to behaviorally important tones. In juvenile animals, cortical map plasticity in the
ACx can be induced by passive environmental enrichment with a certain sound. In rodents, juvenile cortical
map plasticity is limited to a few postnatal days (i.e., the early critical period). In mature animals, cortical map
plasticity can be induced only if tones are behaviorally important or paired with the activation of modulatory
(e.g., cholinergic, dopaminergic, noradrenergic) projections. During the previous funding period, we determined
that cortical map plasticity is encoded by the same mechanisms as long-term potentiation (LTP) and long-term
depression (LTD) at thalamocortical (TC) excitatory synapses. TC projections are the major sensory input to
the neocortex and contribute to the formation of cortical maps. In brain slices, we showed that TC synaptic
plasticity is not lost after the early critical period, instead a gating mechanism is acquired that can be released
by activating cholinergic receptors on presynaptic terminals. Once gating is released, LTP/LTD at TC synapses
and cortical map plasticity in vivo occur in animals aged beyond the early critical period. Adenosine machinery,
consisting of adenosine-producing ecto-5'-nucleotidase (Nt5e) and A1 adenosine receptors (A1Rs), provides
the gating. Juvenile plasticity can be reestablished in adults, if acoustic stimuli are paired with disruption of
Nt5e or A1R signaling in the auditory thalamus. This plasticity occurs in cortical maps and individual ACx
neurons of awake adult mice and is associated with long-term improvement in tone-discrimination abilities. In
this competitive renewal, we propose to test our hypothesis that the adenosine machinery in the thalamus is
the master mediator that transmits information from modulatory projections to the thalamus during ACx map
plasticity in adults. In Aim 1, we will induce cortical map plasticity in adults by pairing sounds with activation of
modulatory projections while activating or deactivating the gating mechanism. In Aim 2, we will explore the
molecular mechanisms of terminating the early critical period by investigating age dependency of adenosine
production. In Aim 3, we will determine time scales of the gating mechanisms. Using fast-scan cyclic
voltammetry in awake mice, we found that adenosine is transiently released in the auditory thalamus and
cortex in response to sound. We propose to elucidate the mechanisms and kinetics of this sound-evoked
adenosine release before and after the early critica...

## Key facts

- **NIH application ID:** 10241345
- **Project number:** 5R01DC012833-09
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Stanislav S Zakharenko
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $460,489
- **Award type:** 5
- **Project period:** 2013-07-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241345

## Citation

> US National Institutes of Health, RePORTER application 10241345, Synaptic mechanisms of auditory memory (5R01DC012833-09). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10241345. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*