Feedforward Inhibition of Projection Neurons by Fast-Spiking GABA Interneurons in the Rat StriatumIn Vivo

Abstract

Discharge activities and local field potentials were recorded in the orofacial motor cortex and in the corresponding rostrolateral striatum of urethane-anesthetized rats. Striatal projection neurons were identified by antidromic activation and fast-spiking GABAergic interneurons (FSIs) by their unique characteristics: briefer spike and burst responses. Juxtacellular injection of neurobiotin combined with parvalbumin immunohistochemistry validated this identification. Spontaneous activities and spike responses to cortical stimulation were recorded during both states of cortical activity: slow waves and desynchronization. Both FSI and projection neurons spontaneously discharged synchronously with slow waves at the maximum of cortical activity, but, on average, FSIs were much more active. Cortical desynchronization enhanced FSI activity and facilitated their spike responses to cortical stimulation, whereas opposite effects were observed regarding projection neurons. Experimental conditions favoring FSI discharge were always associated with a decrease in the firing activity of projection neurons. Spike responses to cortical stimulation occurred earlier (latency difference, 4.6 ms) and with a lower stimulation current for FSIs than for projection neurons. Moreover, blocking GABA A receptors by local picrotoxin injection enhanced the spike response of projection neurons, and this increase was larger in experimental conditions favoring FSI responses. Therefore, on average, FSIs exert in vivo a powerful feedforward inhibition on projection neurons. However, a few projection neurons were actually more sensitive to cortical stimulation than FSIs. Moreover, picrotoxin, which revealed FSI inhibition, preferentially affected projection neurons exhibiting the weakest sensitivity to cortical stimulation. Thus, feedforward inhibition by FSIs filters cortical information effectively transmitted by striatal projection neurons.

Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

“…Nonetheless, the approach we took has some substantial limitations. Although multiple, strong lines of evidence indicate that the brief-waveform striatal neurons are FSIs (discussed in Berke et al, 2004;Mallet et al, 2005), this identification cannot be made with certainty using extracellular recording alone. We cannot readily establish whether the observed activity changes were the cause of altered behavior, or merely a correlate.…”

“…As in our previous studies using other data sets (Berke, 2008;Berke et al, 2004;Gage et al, 2008), we found clearly separate groups of striatal neurons (Figure 1a and b). The group with extremely brief waveforms was presumed to be PV + FSIs, on the basis of the brief waveforms of such cells in previous in vitro and anesthetized in vivo studies (Kawaguchi, 1993;Mallet et al, 2005), and the known intrastriatal distribution and firing patterns of FSIs (discussed in Berke et al, 2004). The large group of cells with longer-duration waveforms was presumed to be MSNs; these cells typically had much lower mean firing rates (in no case 410 Hz) and were not tonically active (not shown).…”

“…Parvalbumin-positive (PV + ) fast-spiking interneurons (FSIs) form a major striatal cell class that has come under increasing recent scrutiny. Both in vitro and anesthetized in vivo studies have shown that FSIs can provide powerful perisomatic inhibition of MSNs (Koos and Tepper, 1999;Mallet et al, 2005), whereas studies in behaving animals (Berke, 2008;Berke, 2009;Gage et al, 2008) and detailed network simulations (for example, Humphries et al, 2009;Moyer and Wolf, 2009) indicate that FSI:MSN interactions are more complex than simple inhibition (see Discussion). The exact role of FSIs in normal striatal information processing is unknown, although there is evidence that they are involved in the suppression of unwanted actions .…”

The Reward Circuit: Linking Primate Anatomy and Human Imaging

“…Here, axons from each area synapse onto single fast spiking GABAergic interneurons. Interestingly, these interneurons are more responsive to cortical input than the medium spiny cells (Charpier et al, 1999;Mallet et al, 2005;Ramanathan et al, 2002;Takada et al, 1998). This suggests a potentially critical role for interneurons to integrate information from different cortical areas before passing that information onto the medium spiny projection cells.…”

Interplay between periodic stimulation and GABAergic inhibition in striatal network oscillations

“…Two of the most examined sources of GABAergic inhibition into MSNs are the feedback inhibition (FB) from the axon collaterals of the MSNs themselves, and the feedforward inhibition (FF) via the small population (1-2% of striatal neurons) of fastspiking interneurons (FSIs) [25][26][27][28]. While feedback inhibition is made up of many weak inputs the feedforward inhibition is powerful, and spiking in a single FSI is capable of significantly delaying spike generation in a large number of postsynaptic medium spiny neurons [29][30][31][32][33][34]. High firing rate and uncorrelated spiking of FSIs may further amplify the effect of feedforward inhibition on the MSNs [35][36].…”