Activation of specific interneurons improves V1 feature selectivity and visual perception

Abstract

Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABAergic interneurons have been identified based on their morphology, molecular markers, biophysical properties, and innervation pattern1,2,3. However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in mouse V1 sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes4,5 and channelrhodopsin 2 (ChR2)-mediated optical activation6, we found that elevated spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than decreased spiking of excitatory neurons, since archaerhodopsin-3 (Arch)-mediated optical silencing7 of calcium/calmodulin-dependent protein kinase IIα-positive (CaMKIIα+) excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, since activating somatostatin (SOM+) or vasointestinal peptide (VIP+) interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by elevated spiking of a specific subtype of cortical inhibitory interneurons.

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

“…For example, Atallah, et al (2012) found that optogenetically activating PV interneurons decreased pyramidal cell activity divisively by a factor of 1.4 and subtracted a constant amount. 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.…”

“…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. They found that the improvement that this produced in orientation discrimination mirrored the sharpened V1 orientation tuning as measured electrophysiologically.…”

Visual mismatch negativity (vMMN): A review and meta-analysis of studies in psychiatric and neurological disorders

“…1 However, the dopamine dysregulation hypothesis does not explain cognitive deficits and negative symptoms. The current view, beside a dysregulation of the dopaminergic system, also incorporates misbalanced glutamatergic and GABAergic (Gamma-aminobutyric acid) neurotransmitters (Marsman et al, 2013) 2 mediating cortical processing (pyramidal cells/interneurons) and supporting the notion of aberrant sensory processing (Lee et al, 2012;Lewis, 2014). In fact, interactions of glutamatergic NMDAR (N-Methyl-D-Aspartate receptor) and dopamine receptors are a key mechanism in multiple pathophysiological theories of schizophrenia (Frohlich & Van Horn, 2014 Q5 ).…”

Interplay between periodic stimulation and GABAergic inhibition in striatal network oscillations

“…Furthermore, by setting a narrow window of spiking FSIs can synchronize the neuronal activity and generate high frequency cortical rhythms [65][66][67]. Finally, by directly projecting to the soma of the neurons, FSIs control the effective gain of the neurons and provide the much needed divisive inhibition and a mechanism of normalization [68][69][70]. In the striatum despite their high firing rates, FSIs do not seem to play a major role in controlling the firing of MSNs [35] and so far it has not been possible to attribute a functional role to FSIs in the striatum.…”