Interneuronal GluK1 kainate receptors control maturation of GABAergic transmission and network synchrony in the hippocampus

Kainate type glutamate receptors (KARs) are strongly expressed in GABAergic interneurons and have the capability of modulating their functions via ionotropic and G-protein coupled mechanisms. GABAergic interneurons are critical for generation of coordinated network activity in both neonatal and adult brain, yet the role of interneuronal KARs in network synchronization remains unclear. Here, we show that GABAergic neurotransmission and spontaneous network activity is perturbed in the hippocampus of neonatal mice lacking GluK1 KARs selectively in GABAergic neurons. Endogenous activity of interneuronal GluK1 KARs maintains the frequency and duration of spontaneous neonatal network bursts and restrains their propagation through the hippocampal network. In adult male mice, the absence of GluK1 in GABAergic neurons led to stronger hippocampal gamma oscillations and enhanced theta-gamma cross frequency coupling, coinciding with faster spatial relearning in the Barnes maze. In females, loss of interneuronal GluK1 resulted in shorter sharp wave ripple oscillations and slightly impaired abilities in flexible sequencing task. In addition, ablation of interneuronal GluK1 resulted in lower general activity and novel object avoidance, while causing only minor anxiety phenotype. These data indicate a critical role for GluK1 containing KARs in GABAergic interneurons in regulation of physiological network dynamics in the hippocampus at different stages of development.Peer reviewe

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

Publisher Copyright: © 2022 The Author(s)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. We report that aberrant prefrontal inputs to basolateral amygdala (BLA) GABAergic interneurons transiently increase the strength of feed-forward inhibition in the BLA, which raises LTP induction threshold in MS treated male rats. The enhanced GABAergic activity after MS exposure associates with lower functional synchronization within prefrontal-amygdala networks in vivo. Intriguingly, no differences in these parameters were detected in females, which were also resistant to MS dependent changes in anxiety-like behaviors. Impaired plasticity and synchronization during the sensitive period of circuit refinement may contribute to long-lasting functional changes in the prefrontal-amygdaloid circuitry that predispose to neuropsychiatric conditions later on in life.Peer reviewe