Paolo Medini

The cerebral cortex is the part of our brain where
sensory information is processed so to guide our daily motor behaviour, and where the most complicated cognitive tasks are performed. The brain cortex is composed by morphologically and functionally distinct cell types that connect with each other and with other brain areas in a very precise way. Connectivity in the cortex is highly layer- and cell-type specific, and this is reflected in the different way a sensory (e.g. visual) stimulus is represented in different cell types (Medini, Neuroscience, 2011). This is also reflected in the fact that the different cell types composing cortical circuits reacts differently to lack of a sensory input (experience-dependent plasticity -e.g. in response to closure of one eye in the part of the visual cortex receiving inputs from both eyes –Medini, Journal of Neuroscience, 2011).

In the lab we investigate how sensory information is processed by the different cell types composing cortical microcircuits (e.g. excitatory vs inhibitory; superficial or deep cortical layers) and how these circuits combine different sensory inputs to guide motor behaviour (multisensory integration) in specialized "association" cortices –whose functioning is still scarcely understood. In particular, we focus on the cellular microcircuits responsible for how different sensory inputs (e.g. visual, tactile and auditory) interact already in primary sensory cortices (that were classically thought to process only one sensory modality –Iurilli et al, Neuron, 2012) and how they are integrated in truly multisensory association cortices (Olcese et al, Neuron, 2013). Importantly, we next aim at understanding the synaptic and molecular mechanisms that modify this circuit organization after brain lesions or sensory deprivations (e.g. blindness or deafness). This knowledge is necessary to promote brain repair as in case of lesions, it is not enough to transplant differentiated neuronal cells, but the latter have to integrate or even re-create this precise microcircuit organization. Importantly, there are different forms of lesion-driven plasticity in the brain: those leading to function recovery (which is adaptive) and those leading to maladaptive consequences (e.g. cortical circuits may become hyperexcitable to some extent after cortical lesions up to the point to trigger seizures). Dissecting the molecular and cellular mediators of "good" and "bad" plasticity after lesions is important because, if the mechanisms are different it will be possible to promote targeted cellular and molecular interventions aimed at promoting "good" plasticity on one side and to counteract "bad", maladaptive plastic changes on the other hand.

Thus, in extreme summary the two topics of interest in the Lab are:
a) connectivity of cortical microcircuits, at both short-range level (within one cortex) and at long-term level (communication between different cortical areas)
b) synaptic and molecular mechanisms of plasticity of these circuits after lesions/sensory deprivations/lack-of-use
To shy new light onto these still elusive but fascinating phenomena, we use a combination of state of the art techniques to investigate cortical circuits in the intact, living brain. In particular, we use and variably combine in vivo patch clamp recordings (Figure 1) with two-photon calcium or cellular imaging as well as optogenetics. We use genetically modified strains that express fluorescent proteins selectively in excitatory or inhibitory cells so to target electrophysiological recordings to identified cell types (Figure 2), and organic or genetically-encoded calcium indicators to perform population functional imaging with cellular resolution (Figure 3), by means of in vivo two-photon microscopy. To understand the circuit function, we need to manipulate the neuronal activity of identified cell types bidirectionally: to this purpose we use viral vectors as well as transgenic strains to attain cell-type specific expression of molecules that allow activation or inhibition of genetically identified neurons with lights of different wavelengths (optogenetics -Figure 4).