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

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.