Structure of a single whisker representation in layer 2 of mouse somatosensory cortex.

Layer (L)2 is a major output of primary sensory cortex that exhibits very sparse spiking, but the structure of sensory representation in L2 is not well understood. We combined two-photon calcium imaging with deflection of many whiskers to map whisker receptive fields, characterize sparse coding, and quantitatively define the point representation in L2 of mouse somatosensory cortex. Neurons within a column-sized imaging field showed surprisingly heterogeneous, salt-and-pepper tuning to many different whiskers. Single whisker deflection elicited low-probability spikes in highly distributed, shifting neural ensembles spanning multiple cortical columns. Whisker-evoked response probability correlated strongly with spontaneous firing rate, but weakly with tuning properties, indicating a spectrum of inherent responsiveness across pyramidal cells. L2 neurons projecting to motor and secondary somatosensory cortex differed in whisker tuning and responsiveness, and carried different amounts of information about columnar whisker deflection. From these data, we derive a quantitative, fine-scale picture of the distributed point representation in L2.

Physiology and Impact of Horizontal Connections in Rat Neocortex.

Cortical information processing at the cellular level has predominantly been studied in local networks, which are dominated by strong vertical connectivity between layers. However, recent studies suggest that the bulk of axons targeting pyramidal neurons most likely originate from outside this local range, emphasizing the importance of horizontal connections. We mapped a subset of these connections to L5B pyramidal neurons in rat somatosensory cortex with photostimulation, identifying intact projections up to a lateral distance of 2 mm. Our estimates of the spatial distribution of cells presynaptic to L5B pyramids support the idea that the majority is located outside the local volume. The synaptic physiology of horizontal connections does not differ markedly from that of local connections, whereas the layer and cell-type-dependent pattern of innervation does. Apart from L2/3, L6A provides a strong source of horizontal connections. Implementing our data into a spiking neuronal network model shows that more horizontal connections promote robust asynchronous ongoing activity states and reduce noise correlations in stimulus-induced activity.

Cortical cellular encoding of thermotactile integration.

Recent evidence suggests that primary sensory cortical regions play a role in the integration of information from multiple sensory modalities. How primary cortical neurons integrate different sources of sensory information is unclear, partly because non-primary sensory input to a cortical sensory region is often weak or modulatory. To address this question, we take advantage of the robust representation of thermal (cooling) and tactile stimuli in mouse forelimb primary somatosensory cortex (fS1). Using a thermotactile detection task, we show that the perception of threshold-level cool or tactile information is enhanced when they are presented simultaneously, compared with presentation alone. To investigate the cortical cellular correlates of thermotactile integration, we performed in vivo extracellular recordings from fS1 in awake resting and anesthetized mice during unimodal and bimodal stimulation of the forepaw. Unimodal stimulation evoked thermal- or tactile- specific excitatory and inhibitory responses of fS1 neurons. The most prominent features of combined thermotactile stimulation are the recruitment of unimodally silent fS1 neurons, non-linear integration features, and response dynamics that favor longer response durations with additional spikes. Together, we identify quantitative and qualitative changes in cortical encoding that may underlie the improvement in perception of thermotactile surfaces during haptic exploration.

Increased Excitation-Inhibition Ratio Stabilizes Synapse and Circuit Excitability in Four Autism Mouse Models.

Distinct genetic forms of autism are hypothesized to share a common increase in excitation-inhibition (E-I) ratio in cerebral cortex, causing hyperexcitability and excess spiking. We provide a systematic test of this hypothesis across 4 mouse models (Fmr1-/y, Cntnap2-/-, 16p11.2del/+, Tsc2+/-), focusing on somatosensory cortex. All autism mutants showed reduced feedforward inhibition in layer 2/3 coupled with more modest, variable reduction in feedforward excitation, driving a common increase in E-I conductance ratio. Despite this, feedforward spiking, synaptic depolarization, and spontaneous spiking were largely normal. Modeling revealed that E and I conductance changes in each mutant were quantitatively matched to yield stable, not increased, synaptic depolarization for cells near spike threshold. Correspondingly, whisker-evoked spiking was not increased in vivo despite detectably reduced inhibition. Thus, elevated E-I ratio is a common circuit phenotype but appears to reflect homeostatic stabilization of synaptic drive rather than driving network hyperexcitability in autism.

Beyond the cortical column: abundance and physiology of horizontal connections imply a strong role for inputs from the surround.

Current concepts of cortical information processing and most cortical network models largely rest on the assumption that well-studied properties of local synaptic connectivity are sufficient to understand the generic properties of cortical networks. This view seems to be justified by the observation that the vertical connectivity within local volumes is strong, whereas horizontally, the connection probability between pairs of neurons drops sharply with distance. Recent neuroanatomical studies, however, have emphasized that a substantial fraction of synapses onto neocortical pyramidal neurons stems from cells outside the local volume. Here, we discuss recent findings on the signal integration from horizontal inputs, showing that they could serve as a substrate for reliable and temporally precise signal propagation. Quantification of connection probabilities and parameters of synaptic physiology as a function of lateral distance indicates that horizontal projections constitute a considerable fraction, if not the majority, of inputs from within the cortical network. Taking these non-local horizontal inputs into account may dramatically change our current view on cortical information processing.

Precisely timed signal transmission in neocortical networks with reliable intermediate-range projections.

The mammalian neocortex has a remarkable ability to precisely reproduce behavioral sequences or to reliably retrieve stored information. In contrast, spiking activity in behaving animals shows a considerable trial-to-trial variability and temporal irregularity. The signal propagation and processing underlying these conflicting observations is based on fundamental neurophysiological processes like synaptic transmission, signal integration within single cells, and spike formation. Each of these steps in the neuronal signaling chain has been studied separately to a great extend, but it has been difficult to judge how they interact and sum up in active sub-networks of neocortical cells. In the present study, we experimentally assessed the precision and reliability of small neocortical networks consisting of trans-columnar, intermediate-range projections (200-1000 mum) on a millisecond time-scale. Employing photo-uncaging of glutamate in acute slices, we activated a number of distant presynaptic cells in a spatio-temporally precisely controlled manner, while monitoring the resulting membrane potential fluctuations of a postsynaptic cell. We found that signal integration in this part of the network is highly reliable and temporally precise. As numerical simulations showed, the residual membrane potential variability can be attributed to amplitude variability in synaptic transmission and may significantly contribute to trial-to-trial output variability of a rate signal. However, it does not impair the temporal accuracy of signal integration. We conclude that signals from intermediate-range projections onto neocortical neurons are propagated and integrated in a highly reliable and precise manner, and may serve as a substrate for temporally precise signal transmission in neocortical networks.