Behaviorally relevant decision coding in primary somatosensory cortex neurons.

Primary sensory cortex is thought to process incoming sensory information, while decision variables important for driving behavior are assumed to arise downstream in the processing hierarchy. Here, we used population two-photon calcium imaging and targeted two-photon optogenetic stimulation of neurons in layer 2/3 of mouse primary somatosensory cortex (S1) during a texture discrimination task to test for the presence of decision signals and probe their behavioral relevance. Small but distinct populations of neurons carried information about the stimulus irrespective of the behavioral outcome (stimulus neurons), or about the choice irrespective of the presented stimulus (decision neurons). Decision neurons show categorical coding that develops during learning, and lack a conclusive decision signal in Miss trials. All-optical photostimulation of decision neurons during behavior improves behavioral performance, establishing a causal role in driving behavior. The fact that stimulus and decision neurons are intermingled challenges the idea of S1 as a purely sensory area, and causal perturbation suggests a direct involvement of S1 decision neurons in the decision-making process.

Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines.

Transgenic mouse lines are invaluable tools for neuroscience but, as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, of either sex, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, although rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

Parvalbumin interneurons provide grid cell-driven recurrent inhibition in the medial entorhinal cortex.

Grid cells in the medial entorhinal cortex (MEC) generate metric spatial representations. Recent attractor-network models suggest an essential role for GABAergic interneurons in the emergence of the grid-cell firing pattern through recurrent inhibition dependent on grid-cell phase. To test this hypothesis, we studied identified parvalbumin-expressing (PV(+)) interneurons that are the most likely candidate for providing this recurrent inhibition onto grid cells. Using optogenetics and tetrode recordings in mice, we found that PV(+) interneurons exhibited high firing rates, low spatial sparsity and no spatial periodicity. PV(+) interneurons inhibited all functionally defined cell types in the MEC and were in turn recruited preferentially by grid cells. To our surprise, we found that individual PV(+) interneurons received input from grid cells with various phases, which most likely accounts for the broadly tuned spatial firing activity of PV(+) interneurons. Our data argue against the notion that PV(+) interneurons provide phase-dependent recurrent inhibition and challenge recent attractor-network models of grid cells.

The columnar and laminar organization of inhibitory connections to neocortical excitatory cells.

The cytoarchitectonic similarities of different neocortical regions have given rise to the idea of 'canonical' connectivity between excitatory neurons of different layers within a column. It is unclear whether similarly general organizational principles also exist for inhibitory neocortical circuits. Here we delineate and compare local inhibitory-to-excitatory wiring patterns in all principal layers of primary motor (M1), somatosensory (S1) and visual (V1) cortex, using genetically targeted photostimulation in a mouse knock-in line that conditionally expresses channelrhodopsin-2 in GABAergic neurons. Inhibitory inputs to excitatory neurons derived largely from the same cortical layer within a three-column diameter. However, subsets of pyramidal cells in layers 2/3 and 5B received extensive translaminar inhibition. These neurons were prominent in V1, where they might correspond to complex cells, less numerous in barrel cortex and absent in M1. Although inhibitory connection patterns were stereotypical, the abundance of individual motifs varied between regions and cells, potentially reflecting functional specializations.