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Circuits for multisensory integration in the perirhinal cortex

Periodic Reporting for period 1 - RhinalMultiSense (Circuits for multisensory integration in the perirhinal cortex)

Periodo di rendicontazione: 2020-05-01 al 2022-04-30

Our actions depend on the continuous processing of information from different senses (e.g. vision, touch, smell). The mechanisms by which the brain combines information from different sensory modalities is called multisensory processing. Multisensory processing allows us to focus our attention on a particular speaker in a crowded room by combining auditory inputs from the speech and visual inputs from the mouth movements. Multisensory processing is fundamental in object recognition, which is the mechanism that allows our brain to recognize objects in the environment and act upon them appropriately. In the context of object recognition, different sensory inputs are combined to create a unique neural representation of objects. However, we can also recognize the same object with different sensory modalities. For example, we can recognize a pencil in our backpack by looking into it (vision) or by searching with our hands (touch). This ability depends on a multisensory representation of the pen in our brain.
The perirhinal cortex is a high order association area involved in object recognition. It receives information from all sensory modalities. The aim of the RhinalMultiSense project was to unveil the circuits of perirhinal cortex involved in sensory and multisensory processing. To achieve this goal, I combined neuroanatomical tracing to map the sensory inputs of perirhinal cortex along its rostro-caudal axis. These experiments revealed the origin of sensory inputs to perirhinal cortex and their topographic organization. I then used in vitro electrophysiology coupled with optogenetics to test the circuits involved in processing tactile inputs in perirhinal cortex.
The results of RhinalMultiSense will be fundamental to resolve the mechanisms of multisensory object recognition in the cortex.
In RhinalMultiSense, I used neuroanatomical tracing methods to map the sensory inputs of the mouse perirhinal cortex. By performing retrograde tracing from different rostro-caudal parts of perirhinal cortex, I found that sensory inputs are topographically organized along its rostro-caudal axis. Somatosensory inputs arising from primary and secondary somatosensory cortex terminate in rostral perirhinal cortex. Visual inputs arising from secondary visual cortex (V2) and postrhinal cortex (POR) terminate in the caudal perirhinal cortex. Rostral perirhinal cortex receives visual inputs mainly from POR, suggesting its role in multisensory processing. Moreover, I found that rostral and caudal perirhinal cortex are extensively interconnected. This pathway might also contribute to multisensory processing and predictive coding.
I performed in vitro electrophysiological recordings couped with optogenetics to test the connectivity between primary somatosensory cortex and perirhinal cortex. I found that somatosensory inputs target preferentially the deep layers in both cerebral hemispheres. Somatosensory inputs had a strong and long-lasting inhibitory component. I found that the largest population of inhibitory neurons in perirhinal cortex does not express any of the known molecular markers for cortical interneurons. I described a viral approach to label these neurons that will allow me to test whether these inhibitory cells mediate the inhibition elicited by somatosensory inputs.
I presented results of the RhinalMultiSense project at the FENS meeting in 2020, at a symposium at the Nencki Institute in Poland, and at a Symposium at the Department of Biotechnology of the University of Pavia, Italy. More information on RhinalMultiSense is available at https://nigrolab.com.
So far, I published two open access peer-reviewed article and one preprint in biorxiv. Another manuscript is currently in preparation and will be submitted to an open access journal and uploaded in biorxiv.
Behavioral work has demonstrated that the perirhinal cortex is fundamental for object recognition depending on multiple sensory modalities. However, the organization of sensory inputs in the perirhinal cortex and the circuits integrating sensory inputs is poorly understood. RhinalMultiSense provides a map of the topographic organization of cortical and thalamic sensory inputs along the rostro-caudal axis of the perirhinal cortex of the mouse. I described an overlooked somatosensory pathway terminating in the rostral perirhinal cortex. This suggests that perirhinal cortex is located at the top of the somatosensory cortical hierarchy. My results further suggest that the recurrent connectivity along the rostro-caudal axis is fundamental in multisensory processing.
RhinalMultiSense provides the first evidence of an inhibitory mechanism in perirhinal cortex gating sensory inputs. Indeed, optogenetic stimulation of somatosensory inputs elicit strong inhibition in the perirhinal cortex of both hemispheres.
These results are currently guiding the efforts in my newly funded Research Group to unveil the mechanisms of sensory and multisensory processing by large neuronal populations in perirhinal cortex.
The Nigro lab is interested in multisensory processing in the cortex