Division and subtraction by distinct cortical inhibitory networks in vivo

Abstract

Brain circuits process information through specialized neuronal subclasses interacting within a network. Revealing their interplay requires activating specific cells while monitoring others in a functioning circuit. Here we use a new platform for two-way light-based circuit interrogation in visual cortex in vivo to show the computational implications of modulating different subclasses of inhibitory neurons during sensory processing. We find that soma-targeting, parvalbumin-expressing (PV) neurons principally divide responses but preserve stimulus selectivity, whereas dendrite-targeting, somatostatin-expressing (SOM) neurons principally subtract from excitatory responses and sharpen selectivity. Visualized in vivo cell-attached recordings show that division by PV neurons alters response gain, whereas subtraction by SOM neurons shifts response levels. Finally, stimulating identified neurons while scanning many target cells reveals that single PV and SOM neurons functionally impact only specific subsets of neurons in their projection fields. These findings provide direct evidence that inhibitory neuronal subclasses have distinct and complementary roles in cortical computations.

On the functions, mechanisms, and malfunctions of intracortical contextual modulation

“…Another optogenetic study found that activating PV inhibitory interneurons sharpened the orientation tuning and direction selectivity of the nearby pyramidal cells to which they were directly connected (Lee, et al, 2012b). In contrast to the findings of Wilson et al (2012), the sharpening was specifically due to PV interneurons because activating SOM and VIP inhibitory interneurons had no such effect. Lee, et al (2012b) showed the relevance of these effects to perceptual discrimination as measured psychophysically by activating PV interneurons in awake mice.…”

“…Selectively reducing their activity reduced surround suppression in Layer 2/3 pyramidal neurons by between 10 and 30% . Furthermore, in accord with their putative role in surround suppression, SOM inhibitory interneurons target dendrites on nearby pyramidal cells with a wide range of orientation specificities (Wilson et al 2012). SOM interneurons are but one of several mechanisms for surround suppression, however, which is also in part inherited from earlier stages of visual processing.…”

“…Some other forms of modulatory suppression are exerted by PV interneurons. Combining optogenetic stimulation with in vivo two-photon imaging in mouse visual cortex Wilson et al (2012) found that activating PV interneurons divisively reduced the slope of a Gaussian function fitted to the spiking of nearby pyramidal cells while leaving the spiking threshold, or offset, unchanged. In contrast to that, activating SOM interneurons had no effect on slope, but it did increase the spiking threshold and sharpen orientation selectivity.…”

Control of response reliability by parvalbumin-expressing interneurons in visual cortex

“…Although one study showed that PV but not SOM activation enhanced stimulus selectivity 22 , another reported that SOM activation sharpened but PV activation preserved selectivity 23 . Although this difference may be due to differences in the protocols of optogenetic activation as well as basic differences in the visual stimuli themselves 22,23,47,48 , our present results demonstrated that both PV and SOM interneurons contribute to response sparseness during natural stimulation.…”

“…Based on the expression of calcium-binding proteins and neuropeptides, interneurons can be classified into distinct groups 14,16,18,19 , among which parvalbumin (PV)-and somatostatin (SOM)-expressing neurons constitute a large fraction 14,19 . Recent studies have used optogenetic techniques to examine how the activities of PV and SOM interneurons influence properties such as cortical response gain, stimulus selectivity and spatial integration [20][21][22][23][24][25] . However, the effect of specific type of inhibitory interneuron on cortical response reliability remains uncharacterized.…”