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Spaeth, L.

Publications and source records attributed to Spaeth, L..

4 recordsLinked to original sources

Medial prefrontal cortex encodes implicit temporal expectations in mice

Temporal prediction allows animals to align their actions with upcoming events, yet most work has focused on explicit duration judgments rather than the implicit timing that shapes ongoing behavior. Here, we ask how medial prefrontal cortex implements such latent temporal expectations and how cerebellar input contributes. Head-fixed mice learned a cued water-delivery task in which reward occurred after either a short or long delay, or after a single fixed delay. During variable delays, running and licking became anticipatory, and medial prefrontal local field potentials and single neurons showed ramping and reward-locked activity patterns aligned to expected reward time. Switching to a fixed delay rapidly sharpened behavioral anticipation and temporal coding. Optogenetic activation of cerebellar Purkinje cells selectively perturbed these dynamics and biased behavior around the earliest possible reward time. These results identify a cerebello-prefrontal circuit that encodes implicit temporal predictions on the sub-second scale.

neuroscience↗

Self-formation of concentric zones of telencephalic and ocular tissues and directional retinal ganglion cell axons

The telencephalon and eye in mammals are originated from adjacent fields at the anterior neural plate. Morphogenesis of these fields generates telencephalon, optic-stalk, optic-disc, and neuroretina along a spatial axis. How these telencephalic and ocular tissues are specified coordinately to ensure directional retinal ganglion cell (RGC) axon growth is unclear. Here, we report the self-formation of human telencephalon-eye organoids comprising concentric zones of telencephalic, optic-stalk, optic-disc, and neuroretinal tissues along the center-periphery axis. Initially-differentiated RGCs grew axons towards and then along a path defined by adjacent PAX2+ optic-disc cells. Single-cell RNA sequencing of CONCEPT organoids not only confirmed telencephalic and ocular identities but also identified expression signatures of early optic-disc, optic-stalk, and RGCs. These signatures were similar to those in human fetal retinas. Optic-disc cells in CONCEPT organoids differentially expressed FGF8 and FGF9; FGFR inhibitions drastically decreased RGC differentiation and directional axon growth. Through the identified RGC-specific cell-surface marker CNTN2, electrophysiologically-excitable RGCs were isolated under a native condition. Our findings provide insight into the coordinated specification of early telencephalic and ocular tissues in humans and establish resources for studying RGC-related diseases such as glaucoma. Impact statementA human telencephalon-eye organoid model that exhibited axon growth and pathfinding from retinal ganglion cell (RGC) axons is reported; via cell surface marker CNTN2 identified using scRNA-seq, early RGCs were isolated under a native condition.

developmental biology↗

Excitation and inhibition delays within a feedforward inhibitory pathway modulate cerebellar Purkinje cell output in mice

The cerebellar cortex computes sensorimotor information from many brain areas through a feedforward inhibitory (FFI) microcircuit between the input stage, the granule cell layer, and the output stage, the Purkinje cells. While in other brain areas FFI underlies a precise excitation vs inhibition temporal correlation, recent findings in the cerebellum highlighted more complex behaviors at the granule cell (GC) - molecular layer interneuron (MLI) - Purkinje cell (PC) FFI pathway. To dissect the temporal organization of the cerebellar FFI pathway, we combined ex vivo patch clamp recordings of PCs with a viral-based strategy to express Channelrhodopsin2 in a subset of mossy fibers (MFs), a major excitatory input to GCs. We show that light-mediated MF activation elicits excitatory and inhibitory currents in PCs with a wide range of temporal delays. Furthermore, in many recordings, excitation and inhibition were initiated by different groups of GCs, expanding PCs synaptic temporal integration. Using a computational model of the FFI pathway we demonstrated that this temporal expansion could strongly influence how PCs integrate MF inputs. Our findings suggest that MF inputs are also encoded by specific delays between excitation and inhibition in PCs.

neuroscience↗

Cerebellar connectivity maps embody individual adaptive behavior

From planification to execution, cerebellar microcircuits encode different features of skilled movements. However, it is unknown whether cerebellar synaptic connectivity maps encode movement features in a motor context specific manner. Here we investigated the spatial organization of excitatory synaptic connectivity in mice cerebellar cortex in different locomotor contexts: during development and in normal, trained or altered locomotor conditions. We combined optical, electrophysiological and graph modelling approaches to describe synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs). Synaptic map maturation during development revealed a critical period in juvenile animals before the establishment of a stereotyped functional organization in adults. However, different locomotor conditions lead to specific GC-PC connectivity maps in PCs. Ultimately, we demonstrated that the variability in connectivity maps directly accounts for individual specific behavioral features of mice locomotion, suggesting that GC-PC networks encode a general motor context as well as individual specific internal models underlying motor adaptation.

neuroscience↗