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Synaptic excitation and inhibition are essential for neuronal communication. However, the variables that regulate synaptic excitation and inhibition in the intact brain remain largely unknown. Here, we examined how spike transmission and suppression between principal cells (PCs) and interneurons (INTs) are modulated by activity history, brain state, cell type, and somatic distance between presynaptic and postsynaptic neurons by applying cross-correlogram analyses to datasets recorded from the dorsal hippocampus and medial entorhinal cortex (MEC) of 11 male behaving and sleeping Long Evans rats. The strength, temporal delay, and brain-state dependency of the spike transmission and suppression depended on the subregions/layers. The spike transmission probability of PC-INT excitatory pairs that showed short-term depression versus short-term facilitation was higher in CA1 and lower in CA3. Likewise, the intersomatic distance affected the proportion of PC-INT excitatory pairs that showed short-term depression and facilitation in the opposite manner in CA1 compared with CA3. The time constant of depression was longer, while that of facilitation was shorter in MEC than in CA1 and CA3. During sharp-wave ripples, spike transmission showed a larger gain in the MEC than in CA1 and CA3. The intersomatic distance affected the spike transmission gain during sharp-wave ripples differently in CA1 versus CA3. A subgroup of MEC layer 3 (EC3) INTs preferentially received excitatory inputs from and inhibited MEC layer 2 (EC2) PCs. The EC2 PC-EC3 INT excitatory pairs, most of which showed short-term depression, exhibited higher spike transmission probabilities than the EC2 PC-EC2 INT and EC3 PC-EC3 INT excitatory pairs. EC2 putative stellate cells exhibited stronger spike transmission to and received weaker spike suppression from EC3 INTs than EC2 putative pyramidal cells. This study provides detailed comparisons of monosynaptic interaction dynamics in the hippocampal-entorhinal loop, which may help to elucidate circuit operations., (© 2024 The Author(s). Hippocampus published by Wiley Periodicals LLC.)

The perirhinal cortex (PER), which is critical for associative memory and stimulus discrimination, has been described as a wall of inhibition between the neocortex and hippocampus. With advanced age, rats show deficits on PER-dependent behavioral tasks and fewer PER principal neurons are activated by stimuli, but the role of PER interneurons in these altered circuit properties in old age has not been characterized. In the present study, PER neurons were recorded while rats traversed a circular track bidirectionally in which the track was either empty or contained eight novel objects evenly spaced around the track. Putative interneurons were discriminated from principal cells based on the autocorrelogram, waveform parameters, and firing rate. While object modulation of interneuron firing was observed in both young and aged rats, PER interneurons recorded from old animals had lower firing rates compared with those from young animals. This difference could not be accounted for by differences in running speed, as the firing rates of PER interneurons did not show significant velocity modulation. Finally, in the aged rats, relative to young rats, there was a significant reduction in detected excitatory and inhibitory monosynaptic connections. Together these data suggest that with advanced age there may be reduced afferent drive from excitatory cells onto interneurons that may compromise the wall of inhibition between the hippocampus and cortex. This circuit dysfunction could erode the function of temporal lobe networks and ultimately contribute to cognitive aging. SIGNIFICANCE STATEMENT We report that lower firing rates observed in aged perirhinal cortical principal cells are associated with weaker interneuron activity and reduced monosynaptic coupling between excitatory and inhibitory cells. This is likely to affect feedforward inhibition from the perirhinal to the entorhinal cortex that gates the flow of information to the hippocampus. This is significant because cognitive dysfunction in normative and pathological aging has been linked to hyperexcitability in the aged CA3 subregion of the hippocampus in rats, monkeys, and humans. The reduced inhibition in the perirhinal cortex reported here could contribute to this circuit imbalance, and may be a key point to consider for therapeutic interventions aimed at restoring network function to optimize cognition., (Copyright © 2017 the authors 0270-6474/17/378965-10$15.00/0.)

Whether the activation of spiking cell ensembles can be encoded in the local field potential (LFP) remains unclear. We address this question by combining in vivo electrophysiological recordings in the rat hippocampus with realistic biophysical modeling, and explore the LFP of place cell sequence spiking ("replays") during sharp wave ripples. We show that multi-site perisomatic LFP amplitudes, in the ∼150-200 Hz frequency band, reliably reflect spatial constellations of spiking cells, embedded within non-spiking populations, and encode activation of local place cell ensembles during in vivo replays. We find spatiotemporal patterns in the LFP, which remain consistent between sequence replays, in conjunction with the ordered activation of place cell ensembles. Clustering such patterns provides an efficient segregation of replay events from non-replay-associated ripples. This work demonstrates how spatiotemporal ensemble spiking is encoded extracellularly, providing a window for efficient, LFP-based detection and monitoring of structured population activity in vivo., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The CA3 and CA1 pyramidal neurons are the major principal cell types of the hippocampus proper. The strongly recurrent collateral system of CA3 cells and the largely parallel-organized CA1 neurons suggest that these regions perform distinct computations. However, a comprehensive comparison between CA1 and CA3 pyramidal cells in terms of firing properties, network dynamics, and behavioral correlations is sparse in the intact animal. We performed large-scale recordings in the dorsal hippocampus of rats to quantify the similarities and differences between CA1 (n > 3,600) and CA3 (n > 2,200) pyramidal cells during sleep and exploration in multiple environments. CA1 and CA3 neurons differed significantly in firing rates, spike burst propensity, spike entrainment by the theta rhythm, and other aspects of spiking dynamics in a brain state-dependent manner. A smaller proportion of CA3 than CA1 cells displayed prominent place fields, but place fields of CA3 neurons were more compact, more stable, and carried more spatial information per spike than those of CA1 pyramidal cells. Several other features of the two cell types were specific to the testing environment. CA3 neurons showed less pronounced phase precession and a weaker position versus spike-phase relationship than CA1 cells. Our findings suggest that these distinct activity dynamics of CA1 and CA3 pyramidal cells support their distinct computational roles., (Copyright © 2011 Wiley Periodicals, Inc.)

Hippocampal sharp waves (SPWs) and associated fast ("ripple") oscillations (SPW-Rs) in the CA1 region are among the most synchronous physiological patterns in the mammalian brain. Using two-dimensional arrays of electrodes for recording local field potentials and unit discharges in freely moving rats, we studied the emergence of ripple oscillations (140-220 Hz) and compared their origin and cellular-synaptic mechanisms with fast gamma oscillations (90-140 Hz). We show that (1) hippocampal SPW-Rs and fast gamma oscillations are quantitatively distinct patterns but involve the same networks and share similar mechanisms; (2) both the frequency and magnitude of fast oscillations are positively correlated with the magnitude of SPWs; (3) during both ripples and fast gamma oscillations the frequency of network oscillation is higher in CA1 than in CA3; and (4) the emergence of CA3 population bursts, a prerequisite for SPW-Rs, is biased by activity patterns in the dentate gyrus and entorhinal cortex, with the highest probability of ripples associated with an "optimum" level of dentate gamma power. We hypothesize that each hippocampal subnetwork possesses distinct resonant properties, tuned by the magnitude of the excitatory drive.

We report that temporal spike sequences from hippocampal place neurons of rats on an elevated track recurred in reverse order at the end of a run, but in forward order in anticipation of the run, coinciding with sharp waves. Vector distances between the place fields were reflected in the temporal structure of these sequences. This bidirectional re-enactment of temporal sequences may contribute to the establishment of higher-order associations in episodic memory.

We investigate the effects of the stochastic nature of ion channels on the faithfulness, precision and reproducibility of electrical signal transmission in weakly active, dendritic membrane under in vitro conditions. The properties of forward and backpropagating action potentials (BPAPs) in the dendritic tree of pyramidal cells are the subject of intense empirical work and theoretical speculation (Larkum et al., 1999; Zhu, 2000; Larkum et al., 2001; Larkum and Zhu, 2002; Schaefer et al., 2003; Williams, 2004; Waters et al., 2005). We numerically simulate the effects of stochastic ion channels on the forward and backward propagation of dendritic spikes in Monte-Carlo simulations on a reconstructed layer 5 pyramidal neuron. We report that in most instances there is little variation in timing or amplitude for a single BPAP, while variable backpropagation can occur for trains of action potentials. Additionally, we find that the generation and forward propagation of dendritic Ca(2+) spikes are susceptible to channel variability. This indicates limitations on computations that depend on the precise timing of Ca(2+) spikes.