Synchronous excitation in the superficial and deep layers of the medial entorhinal cortex precedes early sharp waves in the neonatal rat hippocampus.

Early Sharp Waves (eSPWs) are the earliest pattern of network activity in the developing hippocampus of neonatal rodents. eSPWs were originally considered to be an immature prototype of adult SPWs, which are spontaneous top-down hippocampal events that are self-generated in the hippocampal circuitry. However, recent studies have shifted this paradigm to a bottom-up model of eSPW genesis, in which eSPWs are primarily driven by the inputs from the layers 2/3 of the medial entorhinal cortex (MEC). A hallmark of the adult SPWs is the relay of information from the CA1 hippocampus to target structures, including deep layers of the EC. Whether and how deep layers of the MEC are activated during eSPWs in the neonates remains elusive. In this study, we investigated activity in layer 5 of the MEC of neonatal rat pups during eSPWs using silicone probe recordings from the MEC and CA1 hippocampus. We found that neurons in deep and superficial layers of the MEC fire synchronously during MEC sharp potentials, and that neuronal firing in both superficial and deep layers of the MEC precedes the activation of CA1 neurons during eSPWs. Thus, the sequence of activation of CA1 hippocampal neurons and deep EC neurons during sharp waves reverses during development, from a lead of deep EC neurons during eSPWs in neonates to a lead of CA1 neurons during adult SPWs. These findings suggest another important difference in the generative mechanisms and possible functional roles of eSPWs compared to adult SPWs.

Somatosensory-Evoked Early Sharp Waves in the Neonatal Rat Hippocampus.

The developing entorhinal-hippocampal system is embedded within a large-scale bottom-up network, where spontaneous myoclonic movements, presumably via somatosensory feedback, trigger hippocampal early sharp waves (eSPWs). The hypothesis, that somatosensory feedback links myoclonic movements with eSPWs, implies that direct somatosensory stimulation should also be capable of evoking eSPWs. In this study, we examined hippocampal responses to electrical stimulation of the somatosensory periphery in urethane-anesthetized, immobilized neonatal rat pups using silicone probe recordings. We found that somatosensory stimulation in ~33% of the trials evoked local field potential (LFP) and multiple unit activity (MUA) responses identical to spontaneous eSPWs. The somatosensory-evoked eSPWs were delayed from the stimulus, on average, by 188 ms. Both spontaneous and somatosensory-evoked eSPWs (i) had similar amplitude of ~0.5 mV and half-duration of ~40 ms, (ii) had similar current-source density (CSD) profiles, with current sinks in CA1 strata radiatum, lacunosum-moleculare and DG molecular layer and (iii) were associated with MUA increase in CA1 and DG. Our results indicate that eSPWs can be triggered by direct somatosensory stimulations and support the hypothesis that sensory feedback from movements is involved in the association of eSPWs with myoclonic movements in neonatal rats.