Gamma oscillations are believed to play a critical role in in information processing, encoding, and retrieval. Inhibitory interneuronal network gamma (ING) oscillations may arise from a coupled oscillator mechanism in which individual neurons oscillate or from a population oscillator in which individual neurons fire sparsely and stochastically. All ING mechanisms, including the one proposed herein, rely on alternating waves of inhibition and windows of opportunity for spiking. The coupled oscillator model implemented with Wang-Buzsáki model neurons is not sufficiently robust to heterogeneity in excitatory drive, and therefore intrinsic frequency, to account for in vitro models of ING. Similarly, in a tightly synchronized regime, the stochastic population oscillator model is often characterized by sparse firing, whereas interneurons both in vivo and in vitro do not fire sparsely during gamma, but rather on average every other cycle. We substituted so-called resonator neural models, which exhibit class 2 excitability and postinhibitory rebound (PIR), for the integrators that are typically used. This results in much greater robustness to heterogeneity that actually increases as the average participation in spikes per cycle approximates physiological levels. Moreover, dynamic clampexperimentsthatshowautapse-inducedfiringinentorhinalcorticalinterneuronssupporttheideathatPIRcanserveasanetworkgamma mechanism. Furthermore, parvalbumin-positive (PV ϩ ) cells were much more likely to display both PIR and autapse-induced firing than GAD2 ϩ cells, supporting the view that PV ϩ fast-firing basket cells are more likely to exhibit class 2 excitability than other types of inhibitory interneurons.

Local GABAergic interneurons regulate the activity of spatially-modulated principal cells in the medial entorhinal cortex (MEC), mediating stellate-to-stellate connectivity and possibly enabling grid formation via recurrent inhibitory circuitry. Despite the important role interneurons seem to play in the MEC cortical circuit, the combination of low cell counts and functional diversity has made systematic electrophysiological studies of these neurons difficult. For these reasons, there remains a paucity of knowledge on the electrophysiological profiles of superficial MEC interneuron populations. Taking advantage of glutamic acid decarboxylase 2 (GAD2)-IRES-tdTomato and PV-tdTomato transgenic mice, we targeted GABAergic interneurons for whole-cell patch-clamp recordings and characterized their passive membrane features, basic input/output properties and action potential (AP) shape. These electrophysiologically characterized cells were then anatomically reconstructed, with emphasis on axonal projections and pial depth. K-means clustering of interneuron anatomical and electrophysiological data optimally classified a population of 106 interneurons into four distinct clusters. The first cluster is comprised of layer 2- and 3-projecting, slow-firing interneurons. The second cluster is comprised largely of PV+ fast-firing interneurons that project mainly to layers 2 and 3. The third cluster contains layer 1- and 2-projecting interneurons, and the fourth cluster is made up of layer 1-projecting horizontal interneurons. These results, among others, will provide greater understanding of the electrophysiological characteristics of MEC interneurons, help guide future in vivo studies, and may aid in uncovering the mechanism of grid field formation.

Rapid neck motions can load cervical nerve roots and produce persistent pain. This study investigated the cellular basis of radicular pain and mechanical implications of tissue loading rate. A range of peak loads was applied in an in vivo rat model of dorsal root compression, and mechanical allodynia (i.e. pain) was measured. Axonal damage and nociceptive mediators were assessed in the axons and cell bodies of compressed dorsal roots in separate groups of rats at days 1 and 7 after injury. In the day 7 group, damage in the compressed axons, evaluated by decreased heavy chain neurofilament immunoreactivity, was increased for compressions above a load of 34.08mN, which is similar to the load-threshold for producing persistent pain in that model. Also, the neuropeptide substance P and glial cell line-derived neurotrophic factor and its receptor significantly decreased (p<0.02) with increasing load in the small nociceptive neurons of the dorsal root ganglion, suggesting that axonal damage may also decrease neurotrophic support in injured nociceptive afferent fibers. In a separate study, roots were compressed at 2mm/s, and held, to develop a quasi-linear viscoelastic model that was validated through comparisons to quasistatic loading. The model demonstrated that nearly 23% less displacement was required to reach the axonal injury load threshold during dynamic loading than for quasistatic rates. Together, these studies demonstrate that nerve root compressions that produce pain symptoms are sufficient to mediate nociceptive cellular changes, and that thresholds for pain and nociceptive pathophysiology may be lower for dynamic loading scenarios.

Stellate cells (SCs) of the medial entorhinal cortex exhibit robust spontaneous membrane-potential oscillations (MPOs) in the theta (4–12 Hz) frequency band as well as theta-frequency resonance in their membrane impedance spectra. Past experimental and modeling work suggests that these features may contribute to the phase-locking of SCs to the entorhinal theta rhythm and may be important for forming the hexagonally tiled grid cell place fields exhibited by these neurons in vivo. Among the major biophysical mechanisms contributing to MPOs is a population of persistent (non-inactivating or slowly inactivating) sodium channels. The resulting persistent sodium conductance (GNaP) gives rise to an apparent increase in input resistance as the cell approaches threshold. In this study, we used dynamic clamp to test the hypothesis that this increased input resistance gives rise to voltage-dependent, and thus MPO phase-dependent, changes in the amplitude of excitatory and inhibitory post-synaptic potential (PSP) amplitudes. We find that PSP amplitude depends on membrane potential, exhibiting a 5–10% increase in amplitude per mV depolarization. The effect is larger than—and sums quasi-linearly with—the effect of the synaptic driving force, V – Esyn. Given that input-driven MPOs 10 mV in amplitude are commonly observed in MEC stellate cells in vivo, this voltage- and phase-dependent synaptic gain is large enough to modulate PSP amplitude by over 50% during theta-frequency MPOs. Phase-dependent synaptic gain may therefore impact the phase locking and phase precession of grid cells in vivo to ongoing network oscillations.