Neonatal Restriction of Tactile Inputs Leads to Long-Lasting Impairments of Cross-Modal Processing.

Optimal behavior relies on the combination of inputs from multiple senses through complex interactions within neocortical networks. The ontogeny of this multisensory interplay is still unknown. Here, we identify critical factors that control the development of visual-tactile processing by combining in vivo electrophysiology with anatomical/functional assessment of cortico-cortical communication and behavioral investigation of pigmented rats. We demonstrate that the transient reduction of unimodal (tactile) inputs during a short period of neonatal development prior to the first cross-modal experience affects feed-forward subcortico-cortical interactions by attenuating the cross-modal enhancement of evoked responses in the adult primary somatosensory cortex. Moreover, the neonatal manipulation alters cortico-cortical interactions by decreasing the cross-modal synchrony and directionality in line with the sparsification of direct projections between primary somatosensory and visual cortices. At the behavioral level, these functional and structural deficits resulted in lower cross-modal matching abilities. Thus, neonatal unimodal experience during defined developmental stages is necessary for setting up the neuronal networks of multisensory processing.

Visual-tactile processing in primary somatosensory cortex emerges before cross-modal experience.

The presumptive unisensory neocortical areas process multisensory information by oscillatory entrainment of neuronal networks via direct cortico-cortical projections. While neonatal unimodal experience has been identified as necessary for setting up the neuronal networks of multisensory processing, it is still unclear whether early cross-modal experience equally controls the ontogeny of multisensory processing. Here, we assess the development of visual-somatosensory interactions and their anatomical substrate by performing extracellular recordings of network activity in primary sensory cortices in vivo and assessing the cortico-cortical connectivity in pigmented rats. Similar to adult animals, juvenile rats with minimal cross-modal experience display supra-additive augmentation of evoked responses, time-dependent modulation of power and phase reset of network oscillations in response to cross-modal light and whisker stimulation. Moreover, the neuronal discharge of individual neurons is stronger coupled to theta and alpha network oscillations after visual-tactile stimuli. The adult-like multisensory processing of juvenile rats relies on abundant direct visual-somatosensory connections and thalamocortical feedforward interactions. Thus, cellular and network interactions ensuring multisensory processing emerge before cross-modal experience and refine during juvenile development.

Oscillatory entrainment of primary somatosensory cortex encodes visual control of tactile processing.

Optimal behavior relies on the successful integration of complementary information from multiple senses. The neural mechanisms underlying multisensory interactions are still poorly understood. Here, we demonstrate the critical role of neural network oscillations and direct connectivity between primary sensory cortices in visual-somatosensory interactions. Extracellular recordings from all layers of the barrel field in Brown Norway rats in vivo showed that bimodal stimulation (simultaneous light flash and whisker deflection) augmented the somatosensory-evoked response and changed the power of induced network oscillations by resetting their phase. Anatomical tracing revealed sparse direct connectivity between primary visual (V1) and somatosensory (S1) cortices. Pharmacological silencing of V1 diminished but did not abolish cross-modal effects on S1 oscillatory activity, while leaving the early enhancement of the evoked response unaffected. Thus, visual stimuli seem to impact tactile processing by modulating network oscillations in S1 via corticocortical projections and subcortical feedforward interactions.

Rate and Temporal Coding Convey Multisensory Information in Primary Sensory Cortices.

Optimal behavior and survival result from integration of information across sensory systems. Modulation of network activity at the level of primary sensory cortices has been identified as a mechanism of cross-modal integration, yet its cellular substrate is still poorly understood. Here, we uncover the mechanisms by which individual neurons in primary somatosensory (S1) and visual (V1) cortices encode visual-tactile stimuli. For this, simultaneous extracellular recordings were performed from all layers of the S1 barrel field and V1 in Brown Norway rats in vivo and units were clustered and assigned to pyramidal neurons (PYRs) and interneurons (INs). We show that visual-tactile stimulation modulates the firing rate of a relatively low fraction of neurons throughout all cortical layers. Generally, it augments the firing of INs and decreases the activity of PYRs. Moreover, bimodal stimulation shapes the timing of neuronal firing by strengthening the phase-coupling between neuronal discharge and theta-beta band network oscillations as well as by modulating spiking onset. Sparse direct axonal projections between neurons in S1 and V1 seem to time the spike trains between the two cortical areas and, thus, may act as a substrate of cross-modal modulation. These results indicate that few cortical neurons mediate multisensory effects in primary sensory areas by directly encoding cross-modal information by their rate and timing of firing.

Unraveling Cross-Modal Development in Animals: Neural Substrate, Functional Coding and Behavioral Readout.

The interaction of every living organism with its environment relies on sensory abilities. Hence, sensory systems need to develop rapidly and early in life to guarantee an individual's survival. Sensors have to emerge that are equipped with receptors that detect a variety of stimuli. These sensors have to be wired in basic interconnected networks that possess the ability to process the uni- as well as multisensory information encoded in the sensory input. Plastic changes to refine and optimize these circuits need to be effected quickly during periods of sensory experience so that uni- and multisensory systems can rapidly achieve the functional maturity needed to support the perceptual and behavioral functions reliant upon them. However, the requirement that sensory abilities mature quickly during periods of enhanced neuroplasticity is at odds with the complexity of sensory networks. Neuronal assemblies within sensory networks must be precisely wired so that processing and coding mechanisms can render relevant stimuli more salient and bind features together appropriately. Focusing on animal research, the first part of this review describes mechanisms of sensory processing that show a high degree of similarity within and between sensory systems and highlight the network complexity in relationship to the temporal and spatial precision that is needed for optimal coding and processing of sensory information. Given the resemblance of most adult intra- and intersensory coding mechanisms, it is likely that their developmental principles are similar. The second part of the review focuses on developmental aspects, summarizing the mechanisms underlying the emergence and refinement of precisely coordinated neuronal and multisensory functioning. For this purpose, we review animal research that elucidates the neural substrate of multisensory development applicable to, the less accessible, human development. Animal studies in this field have not only complemented human studies, but brought new ideas and numerous cutting edge conclusions leading to the discovery of common principles and mechanisms.

Oscillatory activity in developing prefrontal networks results from theta-gamma-modulated synaptic inputs.

The hippocampus-driven entrainment of neonatal prefrontal circuits in theta-gamma oscillations contributes to the maturation of cognitive abilities, yet the underlying synaptic mechanisms are still unknown. Here we combine patch-clamp recordings from morphologically and neurochemically characterized layer V pyramidal neurons and interneurons in vivo, with extracellular recordings from the prelimbic cortex (PL) of awake and lightly anesthetized neonatal rats, to elucidate the synaptic framework of early network oscillations. We demonstrate that all neurons spontaneously fire bursts of action potentials. They receive barrages of fast and slow glutamatergic as well as GABAergic synaptic inputs. Oscillatory theta activity results from long-range coupling of pyramidal neurons, presumably within prelimbic-hippocampal circuits, and from local interactions between interneurons. In contrast, beta-low gamma activity requires external glutamatergic drive on prelimbic interneurons. High-frequency oscillations in layer V are independent of interactions at chemical synapses. Thus, specific theta-gamma-modulated synaptic interactions represent the substrate of network oscillations in the developing PL.