Biology subjects

Trapani, F.

Publications and source records attributed to Trapani, F..

5 recordsLinked to original sources

bioRxiv2025

The Rod Bipolar Cell Pathway Contributes To Surround Responses In OFFRetinal Ganglion Cells

Sensory neurons can be influenced by stimuli beyond their receptive field center, yet the mechanisms underlying this surround modulation remain poorly understood. In the retina, many OFF ganglion cells exhibit responses to ON stimulation outside their receptive field center. However, disentangling the pathways and cell types contributing to these responses has been challenging with traditional experimental approaches. Here, we combined optogenetics, two-photon holographic stimulation, and multi-electrode array recordings to identify the intermediate retinal cell types involved in this circuit. We found that the pathway formed by rod bipolar cells and AII amacrine cells--one of the primary relays of rod-driven signals under low-light conditions--plays a key role in mediating this surround modulation. Specifically, crossover inhibition exploits the same amacrine cells responsible for surround suppression to disinhibit distant ganglion cells. This suggests that the retina repurposes existing circuits for surround modulation, optimizing resources through multifunctional inhibitory pathways.

neuroscience↗

bioRxiv2023

Combined KRASG12C and SOS1 inhibition enhances and extends the anti-tumor response in KRASG12C-driven cancers by addressing intrinsic and acquired resistance

Efforts to improve the anti-tumor response to KRASG12C targeted therapy have benefited from leveraging combination approaches. Here, we compare the anti-tumor response induced by the SOS1-KRAS interaction inhibitor, BI-3406, combined with a KRASG12C inhibitor (KRASG12Ci) to those induced by KRASG12Ci alone or combined with SHP2 or EGFR inhibitors. In lung cancer and colorectal cancer (CRC) models, BI-3406 plus KRASG12Ci induces an anti-tumor response stronger than that observed with KRASG12Ci alone and comparable to those by the other combinations. This enhanced anti-tumor response is associated with a stronger and extended suppression of RAS-MAPK signaling. Importantly, BI-3406 plus KRASG12Ci treatment delays the emergence of acquired adagrasib resistance in both CRC and lung cancer models and is associated with re-establishment of anti-proliferative activity in KRASG12Ci-resistant CRC models. Our findings position KRASG12C plus SOS1 inhibition therapy as a promising strategy for treating both KRASG12C-mutated tumors as well as for addressing acquired resistance to KRASG12Ci.

cancer biology↗

bioRxiv2022

Optogenetic Targeting of AII Amacrine Cells restores Retinal Computations performed by the Inner Retina

Most inherited retinal dystrophies display progressive photoreceptor cell degeneration leading to severe visual impairment. Optogenetic reactivation of inner retinal neurons is a promising avenue to restore vision in retinas having lost their photoreceptors. Expression of optogenetic proteins in surviving ganglion cells, the retinal output, allows them to take on the lost photoreceptive function. Nonetheless, this creates an exclusively ON retina by expression of depolarizing optogenetic proteins in all classes of ganglion cells, whereas a normal retina extracts several features from the visual scene, with different ganglion cells detecting light increase (ON) and light decrease (OFF). Refinement of this therapeutic strategy should thus aim at restoring these computations. In an attempt to do so, we used a promoter that targets gene expression to a specific interneuron of the retina called the AII amacrine cell. The AII amacrine cell simultaneously activates the ON pathway and inhibits the OFF pathway. We show that the optogenetic stimulation of AII amacrine cells allows restoration of both ON and OFF responses in the retina, but also mediates other types of retinal processing such as sustained and transient responses. Targeting amacrine cells with optogenetics is thus a promising avenue to restore better retinal function and visual perception in patients suffering from retinal degeneration.

neuroscience↗

bioRxiv2022

Differences in non-linearities determine retinal cell types

Classifying neurons in different types is still an open challenge. In the retina, recent works have taken advantage of the ability to record a large number of cells to classify ganglion cells into different types based on functional information. While the first attempts in this direction used the receptive field properties of each cell to classify them, more recent approaches have proposed to cluster ganglion cells directly based on their response to standard stimuli. These two approaches have not been compared directly. Here we recorded the responses of a large number of ganglion cells and compared two methods for classifying them into types, one based on the receptive field properties, and the other one using their responses to standard stimuli. We show that the stimulus-based approach allows separating more types than the receptive field-based method, leading to a better classification. This better granularity is due to the fact that the stimulus-based method takes into account not only the linear part of ganglion cell function, but also non-linearities. A careful characterization of non-linear processing is thus key to allow functional classification of sensory neurons.

neuroscience↗

bioRxiv2019

All-optical interrogation of a direction selective retinal circuit by holographic wave front shaping

Direction selective (DS) ganglion cells (GC) in the retina maintain their tuning across a broad range of light levels. Yet very different circuits can shape their responses from bright to dim light, and their respective contributions are difficult to tease apart. In particular, the contribution of the rod bipolar cell (RBC) primary pathway, a key player in dim light, is unclear. To understand its contribution to DSGC response, we designed an all-optical approach allowing precise manipulation of single retinal neurons. Our system activates single cells in the bipolar cell (BC) layer by two-photon (2P) temporally focused holographic illumination, while recording the activity in the ganglion cell layer by 2P Ca2 imaging. By doing so, we demonstrate that RBCs provide an asymmetric input to DSGCs, suggesting they contribute to their direction selectivity. Our results suggest that every circuit providing an input to direction selective cells can generate direction selectivity by itself. This hints at a general principle to achieve robust selectivity in sensory areas.

neuroscience↗