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Frequency-Dependent Synaptic Dynamics Differentially Tune CA1 and CA2 Pyramidal Neuron Responses to Cortical Input.

Qian Sun1,2, Eric W Buss3, Yu-Qiu Jiang2

  • 1Department of Neuroscience, Kavli Institute for Brain Science, Mortimer B. Zuckerman Mind Brain Behavior Institute, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York 10027 qxs111@case.edu sas8@columbia.edu.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|August 13, 2021
PubMed
Summary

Hippocampal CA1 and CA2 neurons respond differently to entorhinal cortex input. CA2 neurons excite strongly to single stimuli, while CA1 neurons preferentially respond to bursts of stimuli, depending on NMDAR activation.

Keywords:
CA1CA2NMDARhippocampusperforant pathsynaptic

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Area of Science:

  • Neuroscience
  • Synaptic Plasticity
  • Hippocampal Circuitry

Background:

  • Entorhinal cortex (EC) projections to hippocampal CA1 and CA2 pyramidal neurons are critical for memory.
  • Previous research indicated CA2 neurons exhibit stronger excitation than CA1 neurons from EC input due to dendritic properties.

Purpose of the Study:

  • To investigate how presynaptic firing rate influences the differential efficacy of EC input onto CA1 and CA2 pyramidal neurons.
  • To elucidate the role of N-methyl-D-aspartate receptors (NMDARs) in mediating these frequency-dependent responses.

Main Methods:

  • Electrophysiological recordings in mice of both sexes.
  • Stimulation of perforant path (PP) inputs with single pulses and high-frequency trains.
  • Pharmacological blockade of NMDARs.

Main Results:

  • A single PP stimulus evoked a 5-6 fold greater EPSP in CA2 compared to CA1.
  • High-frequency PP stimulation induced strong synaptic facilitation in CA1 but not CA2.
  • NMDAR blockade significantly reduced temporal summation in CA1, with minimal effect in CA2.

Conclusions:

  • The efficacy of EC input onto CA1 and CA2 neurons is critically dependent on presynaptic firing rate.
  • CA2 neurons are preferentially activated by single EC spikes, whereas CA1 neurons are selectively recruited by bursts of activity.
  • Distinct temporal dynamics and NMDAR dependence shape CA1 and CA2 responses to naturalistic EC firing patterns.