Progressive development of synchronous activity in the hippocampal neuronal network is modulated by GluK1 kainate receptors.

Kainate receptors are potent modulators of circuit excitability and have been repeatedly implicated in pathophysiological synchronization of limbic networks. While the role of aberrant GluK2 subunit containing KARs in generation of epileptiform hypersynchronous activity is well described, the contribution of other KAR subtypes, including GluK1 subunit containing KARs remain less well understood. To investigate the contribution of GluK1 KARs in developmental and pathological synchronization of the hippocampal neural network, we used multielectrode array recordings on organotypic hippocampal slices that display first multi-unit activity and later spontaneous population discharges resembling ictal-like epileptiform activity (IEA).

Aberrant cortical projections to amygdala GABAergic neurons contribute to developmental circuit dysfunction following early life stress.

Early life stress (ELS) results in enduring dysfunction of the corticolimbic circuitry, underlying emotional and social behavior. However, the neurobiological mechanisms involved remain elusive. Here, we have combined viral tracing and electrophysiological techniques to study the effects of maternal separation (MS) on frontolimbic connectivity and function in young (P14-21) rats.

Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents.

Early life stress (ELS) is a well-characterized risk factor for mood and anxiety disorders. GABAergic microcircuits in the amygdala are critically implicated in anxiety; however, whether their function is altered after ELS is not known. Here we identify a novel mechanism by which kainate receptors (KARs) modulate feedforward inhibition in the lateral amygdala (LA) and show that this mechanism is downregulated after ELS induced by maternal separation (MS).

GluA4 Dependent Plasticity Mechanisms Contribute to Developmental Synchronization of the CA3-CA1 Circuitry in the Hippocampus.

During the course of development, molecular mechanisms underlying activity-dependent synaptic plasticity change considerably. At immature CA3-CA1 synapses in the hippocampus, PKA-driven synaptic insertion of GluA4 AMPA receptors is the predominant mechanism for synaptic strengthening. However, the physiological significance of the developmentally restricted GluA4-dependent plasticity mechanisms is poorly understood.

NETO1 Guides Development of Glutamatergic Connectivity in the Hippocampus by Regulating Axonal Kainate Receptors.

Kainate-type glutamate receptors (KARs) are highly expressed in the developing brain, where they are tonically activated to modulate synaptic transmission, network excitability and synaptogenesis. NETO proteins are auxiliary subunits that regulate biophysical properties of KARs; however, their functions in the immature brain are not known. Here, we show that NETO1 guides the development of the rodent hippocampal CA3-CA1 circuitry via regulating axonal KARs.

Diurnal variations in depression-like behavior of Wistar and spontaneously hypertensive rats in the kainate model of temporal lobe epilepsy.

The purpose of this study was to explore whether the kainate (KA) model of temporal lobe epilepsy (TLE) can be used as a model of comorbid epilepsy and depression to study diurnal behavioral variations in rats. Development of chronic epilepsy was confirmed by the detection of spontaneous motor seizures (SMS) with video monitoring (24 hours/3-5 months after status epilepticus [SE]). KA-treated spontaneously hypertensive rats (SHRs) exhibited higher seizure frequency than Wistar rats during the light phase in the fourth and fifth months after SE.