Conference Agenda

The perirhinal cortex (PER) is a cortical area interconnected with all sensory cortices and with the memory system, and as such it constitutes a gateway for sensory information to the hippocampal formation. PER is thought to integrate sensory information about objects and relay this information to the lateral entorhinal cortex, through the “what” pathway entering the hippocampus. PER has been shown to provide an inhibitory control on sensory information entering the hippocampal formation, however it still unknown how PER neurons integrate sensory information. We used neuroanatomical tracing to demonstrate the topographical organization of visual and tactile inputs along the rostro-caudal axis of PER. We found that inputs from somatosensory areas target almost exclusively the rostral part of PER. Using in vitro physiology, we show that optogenetic activation of axons from barrel cortex produce a stronger response in layer 5 neurons in PER as well as strong feedforward inhibition. We investigated how PER neurons respond to whisker stimulation by recording neural activity in head-fixed awake mice with Neuropixel probes. Passive stimulation of the whiskers modulated a higher percent of neurons in barrel cortex than in PER. Moreover, a higher proportion of perirhinal neurons were inhibited by whisker deflection as compared to barrel cortex, inline with our in vitro results. Our work demonstrates that PER integrates tactile information from the whiskers and this information is subject to strong inhibitory control in PER.

In this talk, I will present a series of research projects that fill a niche in action and perception by investigating their relationship with other forms of cognition, such as motor imagery, and by putting emphasis on the top-down aspects of neural processing. Specifically, I will review fMRI data from three experiments that span three conceptual themes of my ongoing research interests. First, I will present evidence that tactile information of 3D stimuli can be decoded from the activity patterns within the early visual cortex even though the stimuli were unseen, and, as expected, within the early somatosensory cortex. Second, I will show that action intention can be decoded as early as in the foveal cortex even before participants start to move, and that predictions about the visual consequences of an impending movement and motor preparation differentially modulate the activity pattern in early visual and somatosensory-motor areas. With the third project, I will explain how the neural representations for planning vs. imagining hand movements rely on overlapping but distinct neural substrates. In sum, I aim to show that action is not only a product of the motor system, but rather the unitary output generated by a cascade of neural mechanisms that encompass the perceptual, motor and cognitive domains.

The brain generates models of the external world based upon sensory regularities, enabling us to react whenever a mismatch between sensory expectations and experience is met. In this context, neurons in sensory areas of the neocortex show a progressive decrease of their response to repetitive stimuli (sensory adaptation), and increased activity when unexpected inputs arrive (deviant detection). These mechanisms have been studied in depth in the sensory systems of anaesthetized rodents, but if and how they emerge in the awake somatosensory cortex is less clear. During the talk, I will describe a novel sensory stimulation approach to present sequences of “standard” or “deviant” stimuli to the whiskers of the awake mouse, while carrying out two-photon imaging of neuronal activity in layer 2/3 and 4 of barrel cortex. I will then discuss how analytical strategies based on information theory can help investigate the contribution of both individual neurons and local populations to the processing of familiar and unexpected sensory inputs. The results presented aim to provide new insights into the mechanisms underlying the predictive coding model of cortical function.

Atypical sensory processing is a proposed etiological factor underlying the development of behavioural deficits in autism spectrum disorder (ASD). Patients with Phelan-McDermid Syndrome (PMS), a monogenic form of ASD, often show somatosensory processing dysfunction. The gene involved is SHANK3 that encodes a postsynaptic protein in excitatory synapses. Mice mutants of the SHANK3 gene are generally considered a reliable model for studying ASD-like symptoms relevant to PMS since it displays aberrant whisker-independent texture discrimination and reactivity to tactile stimuli. While behavioral deficits have been extensively described, the neural substrates of tactile sensory processing deficits in PMS are still poorly understood.

One prevalent hypothesis is that individuals with autism may experience changes in how incoming sensory information is processed over the entire cortical surface because of a generalized brain hyper-excitability. Here we tested this hypothesis by using a combination of advanced imaging, genetic engineering and behavioural tests. Wide field calcium imaging of evoked cortical activity was performed during whisker stimulation in Shank3B^+/- and Shank3B^+/+ mice expressing GCaMP7f in excitatory neurons at postnatal day 60.

Results show that the spatiotemporal features of the sensory-evoked cortical response are substantially different in both awake and anesthetized Shank3B^+/- compared to Shank3B^+/+. There is an increased excitability associated with a strong and bilateral hyperconnectivity of the motor cortices induced by whisker stimulation in awake Shank3B^+/- mice. In anesthetized subjects, the secondary response to the stimulus is the most affected, leading to a stronger and widespread late activation predominantly in the barrel field. Since the secondary response is associated with the perception of sensory stimuli, this aberrant and enduring activation suggests that perception of the stimulus is altered (and likely longer lasting) in Shank3B^+/- mice. We are currently testing the efficacy of modulating the sensory-evoked activity using transcranial Direct Current Stimulation (tDCS) to rescue the sensory deficits.