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Rossi, L. F.

Publications and source records attributed to Rossi, L. F..

4 recordsLinked to original sources

A causal spatial role for apical dendrites in the cortex

Cortical pyramidal neurons project a long apical dendrite to layer 1 (L1), to receive synaptic inputs that are thought to provide contextual and possibly suppressive modulation. In visual cortex, these inputs are thought to drive or suppress the responses to large stimuli. Here, we demonstrate a causal role for individual apical dendrites in the awake cortex. We performed two-photon assisted dendritic pruning in individual L5 neurons of the mouse primary visual cortex and discovered that apical dendrites do not suppress the responses to large stimuli; rather, they drive the responses of neurons that prefer such stimuli. To establish the synaptic basis of this effect, we imaged the excitatory synaptic inputs targeting the apical dendrite. We found that these inputs cover an extensive region, which is largest in neurons that prefer large stimuli. These results reveal a clear spatial role for apical dendrites in the cortex. HighlightsO_LIOptical dendritic pruning in V1 reveals a causal role for L5 apical dendrites C_LIO_LIApical dendrites drive responses in neurons that prefer large visual stimuli C_LIO_LIImaging of synaptic inputs to apical dendrites reveals extended apical receptive field C_LIO_LIThe apical receptive field is larger in L5 neurons that prefer large visual stimuli C_LI

neuroscience↗

Logic of brain-wide connections with the cerebellar cortex

The cerebellum governs movement and cognition through multiple lobules that carry distinct signals and connect to distinct long-range brain networks. How these specialized computations are reconciled with the brain-wide convergence required for coherent behaviour is unknown, in part because the input-output connectivity of functionally distinct lobules has not been mapped. We combined anterograde and retrograde transsynaptic viral tracing with whole-brain two-photon tomography to map the monosynaptic and disynaptic inputs and outputs of Lobule V (LV) and Simplex (LS), two lobules preferentially involved in movement and reward, respectively. Monosynaptic connectivity was strongly segregated: LV and LS received climbing fiber and mossy fiber inputs from largely non-overlapping source regions and projected to distinct targets within the cerebellar nuclei. In contrast, disynaptic inputs to LV- and LS-projecting olivary neurons arose from a shared set of forebrain, midbrain, and hindbrain regions, with the segregation re-emerging at the level of fine-scale spatial topography within these regions. Disynaptic outputs through the cerebellar nuclei likewise overlapped more than the monosynaptic projections to the nuclei themselves. These findings reveal that overlapping brain-wide pathways interface with locally specialized monosynaptic cerebellar pathways. This organizational logic could support distinct movement- and reward-related computations in the cerebellum while distributing outputs to shared downstream networks, providing an architectural substrate for both segregating and integrating cerebellar motor and cognitive functions.

neuroscience↗

Glutamate indicators with increased sensitivity and tailored deactivation rates

Identifying the input-output operations of neurons requires measurements of synaptic transmission simultaneously at many of a neurons thousands of inputs in the intact brain. To facilitate this goal, we engineered and screened 3365 variants of the fluorescent protein glutamate indicator iGluSnFR3 in neuron culture, and selected variants in the mouse visual cortex. Two variants have high sensitivity, fast activation (< 2 ms) and deactivation times tailored for recording large populations of synapses (iGluSnFR4s, 153 ms) or rapid dynamics (iGluSnFR4f, 26 ms). By imaging action-potential evoked signals on axons and visually-evoked signals on dendritic spines, we show that iGluSnFR4s/4f primarily detect local synaptic glutamate with single-vesicle sensitivity. The indicators detect a wide range of naturalistic synaptic transmission, including in the vibrissal cortex layer 4 and in hippocampal CA1 dendrites. iGluSnFR4 increases the sensitivity and scale (4s) or speed (4f) of tracking information flow in neural networks in vivo.

neuroscience↗

Excitatory and inhibitory intracortical circuits for orientation and direction selectivity

The computations performed by a neuron arise from the functional properties of the circuits providing its synaptic inputs. A prime example of these computations is the selectivity of primary visual cortex (V1) for orientation and motion direction. V1 neurons in layer 2/3 (L2/3) receive input mostly from intracortical circuits1, which involve excitation2-9 and inhibition10-12. To understand how an L2/3 neuron achieves its selectivity, therefore, one must characterize the functional organization of both its excitatory and inhibitory presynaptic ensembles. Here we establish this organization, and show how it predicts orientation selectivity and reveals a new cortical circuit for direction selectivity. We identified the presynaptic partners of pyramidal neurons in mouse V1 through rabies monosynaptic tracing1,13, and imaged the functional properties of the postsynaptic neuron and of its presynaptic ensemble. Excitatory presynaptic neurons were predominantly tuned to the postsynaptic neurons preferred orientation. Excitation and inhibition described an inverted Mexican hat, with inhibitory presynaptic neurons densest near the postsynaptic neuron and excitatory ones distributed more distally. Excitation and inhibition also differed in laminar origin: inhibitory presynaptic neurons concentrated in L2/3 while excitatory ones dominated in L4. The distribution of excitatory neurons in visual space was coaxial with the postsynaptic neurons preferred orientation and lay upstream of the neurons preferred direction. Inhibitory presynaptic neurons, instead, clustered more symmetrically around the postsynaptic neuron and favoured locations downstream of its preferred direction. These results demonstrate that L2/3 neurons obtain orientation selectivity from co-tuned neurons in L4 and beyond, and enhance it by contrasting an elongated excitatory input with a concentric inhibitory input. Moreover, L2/3 neurons can obtain direction selectivity through visually offset14 excitation and inhibition. These circuit motifs resemble those seen in the thalamocortical pathway15-20 and in direction selective cells in the retina21,22, suggesting that they are canonical across brain regions.

neuroscience↗