bioRxiv Science⌕ Search

Biology subjects

Mocellin, P.

Publications and source records attributed to Mocellin, P..

3 recordsLinked to original sources

Adapting a two-photon scanning microscope for simultaneous single-photon imaging of an infrared dopamine sensor

We describe a novel method for adapting a two-photon scanning microscope to enable simultaneous detection of two-photon generated visible fluorescence and single-photon generated near-infrared (nIR) fluorescence. In this configuration, nIR fluorescence is routed through a single-mode optical fiber before detection by a photomultiplier tube. This fiber coupling offers two advantages: first, the optical fiber functions as a pinhole aperture, allowing for improved optical sectioning of the nIR signal; second, it minimizes nIR background fluorescence. To validate the effectiveness of this design, we conducted two sets of experiments. First, we compare two fluorescence indicators of the neurotransmitter dopamine: the genetically encoded indicator GRABDA and single walled carbon nanotube based optical nanosensors (nIRCats). Although nIRCats exhibit lower affinity for dopamine than GRABDA, this property allows for identification of high concentration release sites in the striatum. Second, we simultaneously imaged depolarization-induced calcium changes and dopamine release in the retina. Together, these results demonstrate the utility of integrating confocal nIR detection into a two-photon platform for simultaneous functional imaging across complementary spectral channels.

bioengineering↗

Neuronal heterogeneity in the medial septum and diagonal band of Broca: classes and continua

The medial septum and diagonal band of Broca (MSDB) is known for its diverse populations of cholinergic, GABAergic, and glutamatergic neurons, each contributing to various cognitive processes. However, cell-specific manipulations within this region often result in incongruous behavioral outcomes and reach conflicting conclusions, likely because of a hitherto unknown molecular complexity in its cellular landscape. In this study, we employed single-cell RNA sequencing to thoroughly describe the heterogeneity of MSDB neurons. We confirmed previously established neuronal classes, found gene expression gradients within them and revealed genetically defined subclusters. Moreover, we characterized the genetic profiles of these neuronal subclusters and mapped their spatial distribution. Our analysis presents a comprehensive description of the heterogeneity of MSDB neurons, provides marker genes to target them, explains previous paradoxical results, and opens unexplored avenues to study the impact of neuromodulators in the basal forebrain.

neuroscience↗

A hippocampus-accumbens code guides goal-directed appetitive behavior

Neurons in dorsal hippocampus (dHPC) encode a rich repertoire of task-relevant environmental features, while downstream regions such as the nucleus accumbens (NAc) translate this information into task-adaptive behaviors. Yet, the contents of this information stream and their acute role in behavior remain largely unknown. Here, we used in vivo dual-color two-photon imaging to simultaneously record from both large numbers of hippocampal neurons and an identified subpopulation of NAc-projecting neurons during goal-directed navigation towards a hidden reward zone. We found that NAc-projecting neurons contain enriched spatial information and enhanced representations of non-spatial task-relevant behaviors such as deceleration and appetitive licking, both of which could be elicited by optogenetic activation of dHPC terminals in NAc. A generalized linear model revealed enhanced conjunctive coding in NAc-projecting dHPC neurons, improving the identification of the reward zone. We propose that dHPC routes specific reward-related spatial and behavioral state information to guide NAc action selection.

neuroscience↗