Gamma Oscillations Induced by Kainate Receptor Activation in the Entorhinal CortexIn Vitro

Abstract

Gamma frequency (30-80 Hz) oscillations are recordable from human and rodent entorhinal cortex. A number of mechanisms used by neuronal networks to generate such oscillations in the hippocampus have been characterized. However, it is as yet unclear as to whether these mechanisms apply to other anatomically disparate brain regions. Here we show that the medial entorhinal cortex (mEC) in isolation in vitro generates gamma frequency oscillations in response to kainate receptor agonists. Oscillations had the same horizontal and laminar spatiotemporal distribution as seen in vivo and in the isolated whole-brain preparation. Oscillations occurred in the absence of input from the hippocampal formation and did not spread to lateral entorhinal regions. Pharmacological similarities existed between oscillations in the hippocampus and mEC in that the latter were also sensitive to GABAA receptor blockade, barbiturates, AMPA receptor blockade, and reduction in gap junctional conductance. Stellate and pyramidal neuron recordings revealed a large GABAergic input consisting of gamma frequency IPSP trains. Fast spiking interneurons in the superficial mEC generated action potentials at gamma frequencies phase locked to the local field. Stellate cells also demonstrated a subthreshold membrane potential oscillation at theta frequencies that was temporally correlated with a theta-frequency modulation in field gamma power. Disruption in this stellate theta frequency oscillation by the hyperpolarisation activated current (Ih) blocker ZD7288 also disrupted theta modulation of field gamma frequency oscillations. We propose that similar cellular and network mechanisms to those seen in the hippocampus generate and modulate persistent gamma oscillations in the entorhinal cortex.

Differential contribution of kainate receptors to excitatory postsynaptic currents in superficial layer neurons of the rat medial entorhinal cortex

“…In doing so, we demonstrate in a number of ways that KAR EPSCs recorded from the "No Sag", pyramidal neurons in Layer III contributed significantly more to the non-NMDA EPSC than did those recorded from either "Sag" stellate neurons in Layer II or "Intermediate Sag" neurons in Layers II/III. This is intriguing due to the recent observation that KAR activation in Layer III pyramidal neurons, as in the hippocampus (Fisahn et al, 2004), may contribute to slow wave and gamma frequency oscillations in this brain region (Cunningham et al, 2003, Cunningham et al, 2006. Additionally, given the established roles of KARs in mediating excitotoxicity, particularly in CA3 neurons of the hippocampus, we speculate that the greater functional expression of KARs in layer III pyramidal neurons of the mEC may contribute to their selective vulnerability in TLE and animal models of TLE.…”

“…Such oscillations may be an important underlying substrate for information transfer and pathological processes such as epileptogenesis (Bragin et al, 2000). As in the hippocampus (Fisahn et al, 2004), the mEC can generate gamma frequency oscillations in response to agonists of KARs (Cunningham et al, 2003). Additionally, Cunningham et al have recently demonstrated that activation of postsynaptic KARs in layer III pyramidal neurons of the mEC may underlie slow wave oscillations in this brain region (Cunningham et al, 2006).…”

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

“…A non-invasive method used to assess ketamine-activated circuitry in both humans and rodents is the quantitative electroencephalography (qEEG) measurement of gamma-band power, which is dependent upon activation of fast ionotropic excitatory receptors, including AMPA receptors [28][29][30] . We show that, similar to ketamine, (2R,6R)-HNK administration acutely increases gamma power measured via surface electrodes in vivo (Fig.…”

Adolescent Cannabinoid Exposure Permanently Suppresses Cortical Oscillations in Adult Mice

“…The method we used-KA (400 nM) and CCh (20 mM)-reliably produces b and g oscillations in cortical slices (Buhl et al, 1998;Oke et al, 2010) that strongly resemble network synchrony in the intact neocortex (Steriade et al, 1996). KA and CCh promote robust LFP oscillations in vitro by enhancing excitatory drive (Buhl et al, 1998;Cunningham et al, 2003) and activating cholinergic receptors on GABAergic interneurons Gulyás et al, 2010). Coronal brain slices containing medial prefrontal cortex (mPFC) or primary somatosensory cortex (SCx) were prepared from adult mice administered WIN or vehicle during adolescence (Figure 1a).…”