Spatially heterogeneous acetylcholine dynamics in the striatum promote behavioral flexibility

Being able to switch from established choices to new alternatives when conditions change – behavioral flexibility – is essential for survival. Cholinergic signaling in the striatum contributes to such flexible behavior, yet the timing and spatial organization of acetylcholine release during contingency changes remain unclear, limiting conceptual understanding of its role in behavioral flexibility. Using […]

During hibernation, animals enter torpor, a reversible physiological state typically characterised by reductions in core temperature, heart rate and oxygen consumption. Species that enter this hypothermic and hypometabolic state are highly tolerant of ischaemia-reperfusion injury. Consequently, there is a growing interest in utilizing aspects of torpor for clinical applications, such as protection from ischaemia-reperfusion injury […]

The lack of effective therapies for visual restoration in Retinitis pigmentosa and macular degeneration has led to the development of new strategies, such as optogenetics and retinal prostheses. However, visual restoration is poor due to the massive light-evoked activation of retinal neurons, regardless of the segregation of visual information in ON and OFF channels, which is essential […]

Adenine base editors (ABEs) are genome-editing tools that have been harnessed to introduce precise A•T to G•C conversion. The discovery of split genes revealed that all introns contain two highly conserved dinucleotides, canonical “AG” (acceptor) and “GT” (donor) splice sites. ABE can directly edit splice acceptor sites of the adenine (A) base, leading to aberrant […]

Goal-directed navigation in a new environment requires quickly identifying and exploiting important locations. Identifying new goal locations depends on neural computations that rapidly represent locations and connect location information to key outcomes such as food1. However, the mechanisms to trigger these computations at behaviourally relevant locations are not well understood. Here we show that parvalbumin […]

Timed dopamine signals underlie reinforcement learning, favoring neural activity patterns that drive behaviors with positive outcomes. In the striatum, dopamine activates five dopamine receptors (D1R–D5R), which are differentially expressed in striatal neurons. However, the role of specific dopamine receptors in reinforcement is poorly understood. Using our cell-specific D1R photo-agonist, we find that D1R activation in […]