**2. Subcortical and intracortical connectivity between primary sensory areas**

There is anatomical evidence that crossmodal inputs to primary cortical areas can be conveyed through thalamo-cortical or cortico-cortical projection fibers. There is, however, only scarce anatomical evidence for heteromodal convergence from auditory, visual and somatosensory thalamic nuclei to A1, V1 and S1 [6] (gerbil). By contrast, cortico-cortical connections underpinning plurimodal interplay between these cortical areas are well documented. Tract-tracing methods have revealed the existence of visual-somatosensory projections from V2 to areas 1/3b in S1, and somatosensory projections from S2 to A1 [2] (marmoset). Direct corticocortical connections between A1, V1 and S1 have been identified [1, 7] (macaque; cat). It has been shown that V1 projects mainly to S1, but receives a moderate amount of projections from A1 and S1, while A1 sends more projections to V1 than S1, but receives sparse projections from these two areas [8, 9] (mouse). These findings indicate that the connectivity network between A1, S1 and V1 is asymmetric. Overall, both thalamocortical and corticocortical connections may contribute to the occurrence of short-latency responses to heteromodal inputs reported in these area [10–17] (monkey; human).

In the model of hierarchical organization of cortical connectivity, it is generally assumed that feedforward connections convey sensory information to higher order areas, whereas feedback connections modulate neural activity in lower-level cortical areas [18, 19] (macaque; cat). This model is somewhat challenged by retrograde tracing studies investigating the microcircuitry of reciprocal connections between primary cortical areas. These studies have shown that A1 and S1 project in a feedback manner to V1, while V1 to A1 projections are of feedforward type and V1 to S1 are mostly lateral [8, 9] (mouse). In addition, A1 and S1 are linked by reciprocal feedback projections [6] (gerbil). Hence, the available evidence suggests that connection patterns between primary sensory cortices are not at the same levels in the neural network. Furthermore, based on the labeling of reciprocal connections between V1 and S1 and the characterization of the size and laminar density of axonal swellings, it was concluded that S1 receives a stronger driver input fromV1 and that S1 inputs to V1 have a predominant modulatory influence [9] (mouse). Regarding the projections from the auditory cortex to V1, both types of input have been identified with, however, a clear dominance of small caliber axons bearing modulator boutons [8] (mouse).

Somatosensory-auditory interactions have been found at low-level of multisensory integration. Cutaneous responses were recorded in the caudo-medial auditory cortex, with a feedforward laminar activation profile. The initial excitatory response was located in layer 4, then followed by responses in the extragranular laminae (layers 2, 3, 5 and 6), in contrast with feedback and lateral activation profiles beginning in the extragranular laminae [20] (macaque).

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*Interplay between Primary Cortical Areas and Crossmodal Plasticity*

The intricate connectivity between unimodal primary cortical areas favors crossmodal interplay in the early stage of multisensory integration, presumably through feedforward and feedback connections [21] (for a review). The question arises whether heteromodal connections between low-level sensory cortices exert a global modulatory influence on ongoing firing or more selectively contribute to

shaping the neuronal response characteristics in primary sensory areas.

**3. Neurophysiological mechanisms of multimodal integration in** 

Concurrent stimuli of sensory organs coactivate primary cortical areas and generate reciprocal influences contributing to the process of multimodal integration. It is noticeable that the bulk of studies on multisensory integration in early cortical areas have focused on the interplay between the visual and auditory cortices.

Activation of A1 neurons by noise bursts was found to induce GABAergic inhibition of supragranular pyramidal cells in V1, via cortico-cortical connections, leading to a reduced synaptic and spike activity upon bimodal stimulation [10] (mouse). Furthermore, this acoustic stimulation decreased behavioral responses to a dim flash, likely through GABAergic inhibition in V1, as this effect was prevented by acute blockade of GABAA and GABAB receptors. The authors concluded that salient auditory stimuli degrade potentially distracting sensory processing in the visual cortex. This finding was corroborated by an *in vitro* electrophysiological study showing that layer 1 and layer 2/3 inhibitory neurons in V1 receive direct excitatory inputs from A1 [22] (mouse). Along the same lines, intrinsic signal imaging aimed at simultaneously recording visuotopic maps in V1 and tonotopic maps in A1, showed that a high activation of A1 suppresses visually evoked responses in V1 [5] (mouse). As a result, under bimodal stimulation the global effect of auditory inputs to V1 was such that the neuronal firing averaged across all visual orientations was weaker. Nevertheless, the orientation selectivity of V1 excitatory neurons in layer 2/layer 3 was found to be sharpened by concurrent sound signals or optogenetic activation of A1 to V1 projections [22] (mouse). Indeed, auditory signals increased the neuronal responses at the preferred visual orientation, and decreased responses at the orthogonal orientation, with a stronger impact at lower visual contrast. Tracing data showed that axons from A1 layer 5 to V1 neurons mainly terminated in superficial layers and activated layer 1 inhibitory neurons. The sharpening effect was very likely mediated by a combination of inhibitory and disinhibitory circuits, since layer 1 neurons in V1 being excited by sound, they presumably suppressed layer 2/layer 3 pyramidal cell responses, but also inhibited other inhibitory neurons in layer 2/layer 3, thereby globally contributing to increasing the firing rate of the pyramidal cells at their preferred orientation tuning. A two-photon calcium imaging study showed that when visual and auditory stimulus features are temporally congruent, neurons in V1 exhibit a balanced pattern of response enhancement and suppression compared with unimodal visual stimuli. Temporally incongruent tones or white-noise bursts in paired audiovisual stimuli mainly produce suppressive responses across the neuronal population, in particular when the visual stimulus contrast is high [23] (mouse). Neuronal mechanisms of visual–auditory integration appear to be dependent upon the behavioral context. A study investigating the modulation of V1 neurons by auditory stimuli showed no difference in the latency or strength of visual responses in monkeys trained to a passive central

*DOI: http://dx.doi.org/10.5772/intechopen.95450*

**primary sensory areas**

**3.1 Visual-auditory interactions**

*Interplay between Primary Cortical Areas and Crossmodal Plasticity DOI: http://dx.doi.org/10.5772/intechopen.95450*

The intricate connectivity between unimodal primary cortical areas favors crossmodal interplay in the early stage of multisensory integration, presumably through feedforward and feedback connections [21] (for a review). The question arises whether heteromodal connections between low-level sensory cortices exert a global modulatory influence on ongoing firing or more selectively contribute to shaping the neuronal response characteristics in primary sensory areas.
