Coexistence of Excitatory and Inhibitory GABA Synapses in the Cerebellar Interneuron Network

Abstract

Functional GABA synapses are usually assumed to be inhibitory. However, we show here that inhibitory and excitatory GABA connections coexist in the cerebellar interneuron network. The reversal potential of GABAergic currents (E GABA ) measured in interneurons is relatively depolarized and contrasts with the hyperpolarized value found in Purkinje cells (Ϫ58 and Ϫ85 mV respectively). This finding is not correlated to a specific developmental stage and is maintained in the adult animal. E GABA in interneurons is close to the mean membrane potential (Ϫ56.5 mV, as measured with a novel "equal firing potential" method), and both parameters vary enough among cells so that the driving force for GABA currents can be either inward or outward. Indeed, using noninvasive cell-attached recordings, we demonstrate inhibitory, excitatory, and sequential inhibitory and excitatory responses to interneuron stimulation [results obtained both in juvenile (postnatal days 12-14) and subadult (postnatal days 20 -25) animals]. In hyperpolarized cells, single synaptic GABA currents can trigger spikes or trains of spikes, and subthreshold stimulations enhance the responsiveness to subsequent excitatory stimulation over at least 30 msec. We suggest that the coexistence of excitatory and inhibitory GABA synapses could either buffer the mean firing rate of the interneuron network or introduce different types of correlation between neighboring interneurons, or both.

GABAergic Interneurons are Required for Generation of Slow CA1 Oscillation in Rat Hippocampus

“…Another possibility is the excitatory nature of some GABA A receptors. It has been shown that GABA A receptor-mediated synaptic responses are not always inhibitory, and can be excitatory even in adult animals under normal conditions [31][32][33]. Blocking such excitatory GABA A receptors (if they were involved in the oscillation generation in our recordings) could also be responsible for reduction of the CA1 oscillation.…”

Cell-attached voltage-clamp and current-clamp recording and stimulation techniques in brain slices

“…Consequently, neurophysiologists have gone to elaborate measures in order to determine whether GABA-mediated synaptic potentials are hyperpolarizing or depolarizing at rest (e.g. Verheugen et al, 1999;Chavas and Marty, 2003). Although tight-seal cell-attached recording cannot provide the numerical value of the reversal potential of a synaptic event, it does accurately depict the direction of the synaptic potential (i.e.…”

“…The only differences between the equations presented here and those of Mason et al (2005) are the inclusion of the cell membrane resistance (R cell ) and the liquid junction potential (E lj ) between the electrode solution and the bath solution. R cell is included here because Tyzio et al (2003) and Chavas and Marty (2003) have convincingly described how R cell affects the accuracy of the measured membrane potential in perforated patch and whole-cell recordings when there is a finite R seal . The same reasoning applies to cell-attached recordings.…”

“…The equations are in large part from Tyzio et al (2003) and Chavas and Marty (2003), except with the addition of R patch and E* lj . , when E lj = 0 This is the form found in Mason et al (2005), except for the inclusion of R cell in the ratio.…”

GABAergic Excitation in the Basolateral Amygdala

“…Most instances of depolarizing GABA actions during nonpathological states have been reported after intense or prolonged activation of GABA A receptors Nicoll, 1979, 1982;Staley et al, 1995;Kaila et al, 1997), and are thought to result from a breakdown of the chloride gradient, followed by efflux of bicarbonate anions through open GABA A channels (Staley et al, 1995). However, two recent studies have reported increased postsynaptic spiking after single-pulse stimulation of GABAergic neurons in adult cerebellum (Chavas and Marty, 2003) and cortex (Gulledge and Stuart, 2003).…”