# The role of CaV3.1 T-type calcium channels in cognitive functions mediated by the subicular circuitry

> **NIH NIH K01** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $143,195

## Abstract

Abstract
Cognitive deficits associated with multiple psychiatric disorders appear to emerge as a consequence of changes
in synaptic plasticity and neuronal oscillations of the subiculum, the main output structure of the hippocampal
formation. Thus, resolving the mechanisms that regulate subicular network activity is a crucial task in the pursuit
of novel treatment targets. The majority of subicular neurons can generate high-frequency burst firing which,
along with their ideal anatomical location, enable them to serve as a relay center between the hippocampal
formation and cortical structures, most notably the medial prefrontal cortex (mPFC). This tendency of subicular
pyramidal neurons to burst in rhythmic patterns is likely to be critical for processing important cognitive
information. However, ionic currents that regulate the excitability and, consequently, the function of the subicular
network are largely unknown. Low-voltage activated T-type calcium channels (T-channels) are ideally suited for
modulation of neuronal excitability and oscillatory activity. The preliminary patch-clamp data in mice with global
knock-out of CACNA1G (CaV3.1) strongly suggest a crucial role of this T-channel isoform in mediating excitability
of subicular burst firing neurons. Moreover, the lack of CaV3.1 T-channels induces a complete loss of long-term
potentiation (LTP), the best cellular model of memory processing, at the CA1-subiculum synapse. Finally, the
decrease in the power of high-frequency (gamma) oscillations in freely moving CaV3.1 KO mice is accompanied
by impairment of spatial navigation, which was confirmed with the subiculum-specific CACNA1G knock-down.
Therefore, the central hypothesis of this proposal is that CaV3.1 T-channels, by supporting burst firing, regulate
synaptic plasticity and neuronal oscillations in the subiculum, as well as its input to mPFC, thereby modulating
cognitive processing. During the K01 award, three research aims will be evaluated: 1) to investigate whether
CaV3.1 T-channels regulate synaptic plasticity in the subiculum using ex vivo slice preparation, 2) to investigate
whether subicular CaV3.1 T-channels are important for learning and memory in vivo using tissue-specific knock-
down and selective pharmacology, and 3) to investigate whether CaV3.1 T-channels regulate high-frequency
oscillations in the subiculum and neuronal synchronization between the subiculum and mPFC during a
behavioral memory task. To meet his career objectives and the aims of this research project, the applicant
requires additional training in viral-mediated genetic manipulations, in vitro (LTP) and in vivo local field potential,
as well as single-unit recordings. These experiments will provide valuable insights into the function of T-channels
in a specific subicular circuit and underlying neuronal oscillations associated with cognitive processing. By
complementing the applicant’s present expertise in behavioral pharmacology and patch-clamp electrophysio...

## Key facts

- **NIH application ID:** 10406474
- **Project number:** 7K01MH121567-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Srdan Joksimovic
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $143,195
- **Award type:** 7
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406474

## Citation

> US National Institutes of Health, RePORTER application 10406474, The role of CaV3.1 T-type calcium channels in cognitive functions mediated by the subicular circuitry (7K01MH121567-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10406474. Licensed CC0.

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