Brain State Dependent Postinhibitory Rebound in Entorhinal Cortex Interneurons

Abstract

Postinhibitory rebound (PIR) is believed to play an important role in the genesis and maintenance of biological rhythms. While it has been demonstrated during several in vitro studies, in vivo evidence for PIR remains scarce. Here, we report that PIR can be observed in the dorsomedial entorhinal cortex of anesthetized rats, mostly between putatively connected GABAergic interneurons, and that it is more prevalent during the theta (4 -6 Hz) oscillation state than the slow (0.5-2 Hz) oscillation state. Functional inhibition was also found to be brain state and postsynaptic cell type dependent but that alone could not explain this brain state dependence of PIR. A theoretical analysis, using two Fitzhugh-Nagumo neurons coupled to an external periodic drive, predicted that the modulation of a faster spiking rate by the slower periodic drive could account for the brain state dependence of PIR. Model predictions were verified experimentally. We conclude that PIR is cell type and brain state dependent and propose that this could impact network synchrony and rhythmogenesis.

Brain state-dependent neuronal computation

“…However, the expression of PIR did not depend upon the oscillatory activity (theta vs. slow oscillations) in theta-phase unmodulated pairs of putative interneurons (3.4 presynaptic neuron; 3.5 postsynaptic neuron; bottom panel). Modified from (Adhikari et al, 2012 ).…”

“…Hence, the functional consequence of the firing of the presynaptic cell will be an increased or decreased probability of firing for the postsynaptic cells. This mode of information transfer between two neurons can be revealed in vivo by the cross-correlation function (i.e., cross-correlograms, CCG) between their respective spike trains, which quantifies how much the firing of a one neuron is positively or negatively correlated with the firing of the other neuron within a relatively small time window (Csicsvari et al, 1998 ; Bartho et al, 2004 ; Fujisawa et al, 2008 ; Ostojic et al, 2009 ; Quilichini et al, 2010 ; Adhikari et al, 2012 ) (Figure 1B ). CCGs can thus be used to identify putative direct synaptic connections between neurons (Moore et al, 1970 ).…”

Optogenetics: Keep Interpretations Light

“…However, as soon as the light is off, all "inhibited" cells may produce a hugely synchronized firing response due to postinhibitory rebound, for example, if the cells express the h current. Postinhibitory rebound firing occurs in vivo in physiological conditions (Adhikari et al, 2012). In that case, Y would result from the highly synchronized firing of X cells, not their inhibition.…”

Rebound from Inhibition: Self-Correction against Neurodegeneration?

“…For example, in the mutant superoxide dismutase (SOD1) rodent model of motor neuron degeneration and ALS, motor neurons in the spinal cord become persistently hyperexcitable. In addition, these mice show deficits in rhythmic behavior that normally originates in rebound firing [40,41] and which manifests as abnormal ventral root rhythms that correlate with disease pathology [42,43]. Neurodegeneration is also associated with altered network activity in brain regions that regulate sleep (basal forebrain, hippocampus) [44] and breathing [45], both of which involve rhythmic circuits.…”