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Preparation of Parasagittal Slices for the Investigation of Dorsal-ventral Organization of the Rodent Medial Entorhinal Cortex
Published on: March 28, 2012
The perforant path projection to hippocampal area CA1 in the rat hippocampal-entorhinal cortex combined slice
1Department of Neurophysiology, Institute for Physiology at the Charité, Humboldt Universität Berlin, Germany.
Insights
The perforant path to the hippocampus (CA1) primarily activates inhibitory signals, not excitatory ones. This disynaptic inhibition significantly impacts hippocampal function and processing.
Area of Science:
- Neuroscience
- Neurophysiology
- Hippocampal Circuitry
Background:
- The entorhinal cortex is a key input to the hippocampus.
- Perforant path projections to CA1 are crucial for memory formation.
- Understanding CA1 circuit dynamics is essential for cognitive function.
Purpose of the Study:
- To investigate the nature of the perforant path projection to CA1.
- To characterize the excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) evoked by perforant path stimulation.
- To determine the functional significance of perforant path-evoked inhibition in CA1.
Main Methods:
- Used a combined hippocampal-entorhinal slice preparation.
- Removed CA3 and dentate gyrus to isolate the perforant path.
- Employed field potential and intracellular recordings.
- Utilized pharmacological agents like CNQX and bicuculline.
Main Results:
- Perforant path stimulation evoked prominent fast GABAA and slow GABAB IPSPs in CA1 cells.
- CNQX blocked both excitatory and inhibitory responses, suggesting an intermediary excitatory synapse.
- GABAA inhibition was localized to stratum radiatum and effectively reduced CA1 excitability.
- Blockade of fast inhibition increased excitability via NMDA receptor activation.
Conclusions:
- Perforant path inputs primarily activate disynaptic inhibition in CA1.
- This inhibition plays a critical role in regulating hippocampal output.
- Understanding this inhibitory mechanism is vital for both normal cognition and neurological disorders.
Abstract:
1. The perforant path projection from layer III of the entorhinal cortex to CA1 of the hippocampus was studied within a hippocampal-entorhinal combined slice preparation. We prevented contamination from the other main hippocampal pathways by removal of CA3 and the dentate gyrus. 2. Initially the projection was mapped using field potential recordings that suggested an excitatory sink in stratum lacunosum moleculare with an associated source in stratum pyramidale. 3. However, recording intracellularly from CA1 cells, stimulation of the perforant path produced prominent fast GABAA and slow GABAB IPSPs often preceded by small EPSPs. In a small number of cells we observed EPSPs only. 4. CNQX blocked excitatory and inhibitory responses. This indicated the presence of an intervening excitatory synapse between the inhibitory interneurone and the pyramidal cell. 5. Focal bicuculline applications revealed that the major site of GABAA inhibitory input was to stratum radiatum of CA1. 6. The inhibition activated by the perforant path was very effective at reducing simultaneously activated Schaffer collateral mediated EPSPs and suprathreshold-stimulated action potentials. 7. Blockade of fast inhibition increased excitability and enhanced slow inhibition. Both increases relied upon the activation of NMDA receptors. 8. Perforant path inputs activated prominent and effective disynaptic inhibition of CA1 cells. This has significance for the output of hippocampal processing during normal behaviour and also under pathological conditions.
