On-chip fluorescence microscopy with a random microlens diffuser.

We present an on-chip, widefield fluorescence microscope, which consists of a diffuser placed a few millimeters away from a traditional image sensor. The diffuser replaces the optics of a microscope, resulting in a compact and easy-to-assemble system with a practical working distance of over 1.5 mm. Furthermore, the diffuser encodes volumetric information, enabling refocusability in post-processing and three-dimensional (3D) imaging of sparse samples from a single acquisition. Reconstruction of images from the raw data requires a precise model of the system, so we introduce a practical calibration scheme and a physics-based forward model to efficiently account for the spatially-varying point spread function (PSF). To improve performance in low-light, we propose a random microlens diffuser, which consists of many small lenslets randomly placed on the mask surface and yields PSFs that are robust to noise. We build an experimental prototype and demonstrate our system on both planar and 3D samples.

Experience, circuit dynamics, and forebrain recruitment in larval zebrafish prey capture.

Experience influences behavior, but little is known about how experience is encoded in the brain, and how changes in neural activity are implemented at a network level to improve performance. Here we investigate how differences in experience impact brain circuitry and behavior in larval zebrafish prey capture. We find that experience of live prey compared to inert food increases capture success by boosting capture initiation. In response to live prey, animals with and without prior experience of live prey show activity in visual areas (pretectum and optic tectum) and motor areas (cerebellum and hindbrain), with similar visual area retinotopic maps of prey position. However, prey-experienced animals more readily initiate capture in response to visual area activity and have greater visually-evoked activity in two forebrain areas: the telencephalon and habenula. Consequently, disruption of habenular neurons reduces capture performance in prey-experienced fish. Together, our results suggest that experience of prey strengthens prey-associated visual drive to the forebrain, and that this lowers the threshold for prey-associated visual activity to trigger activity in motor areas, thereby improving capture performance.

Specific hippocampal representations are linked to generalized cortical representations in memory.

Memories link information about specific experiences to more general knowledge that is abstracted from and contextualizes those experiences. Hippocampal-cortical activity patterns representing features of past experience are reinstated during awake memory reactivation events, but whether representations of both specific and general features of experience are simultaneously reinstated remains unknown. We examined hippocampal and prefrontal cortical firing patterns during memory reactivation in rats performing a well-learned foraging task with multiple spatial paths. We found that specific hippocampal place representations are preferentially reactivated with the subset of prefrontal cortical task representations that generalize across different paths. Our results suggest that hippocampal-cortical networks maintain links between stored representations for specific and general features of experience, which could support abstraction and task guidance in mammals.

Distinct hippocampal-cortical memory representations for experiences associated with movement versus immobility.

While ongoing experience proceeds continuously, memories of past experience are often recalled as episodes with defined beginnings and ends. The neural mechanisms that lead to the formation of discrete episodes from the stream of neural activity patterns representing ongoing experience are unknown. To investigate these mechanisms, we recorded neural activity in the rat hippocampus and prefrontal cortex, structures critical for memory processes. We show that during spatial navigation, hippocampal CA1 place cells maintain a continuous spatial representation across different states of motion (movement and immobility). In contrast, during sharp-wave ripples (SWRs), when representations of experience are transiently reactivated from memory, movement- and immobility-associated activity patterns are most often reactivated separately. Concurrently, distinct hippocampal reactivations of movement- or immobility-associated representations are accompanied by distinct modulation patterns in prefrontal cortex. These findings demonstrate a continuous representation of ongoing experience can be separated into independently reactivated memory representations.

Dynamic Hippocampal Circuits Support Learning- and Memory-Guided Behaviors.

The ability to learn spatial relationships and to modify stored representations when the world changes is essential for survival. In recent years, our understanding of the neural activity that underlie these learning and memory processes has improved considerably, in large part to an increase in the number of studies that use electrophysiological recordings as animals learn about their environments. In this review, we summarize some key findings from our laboratory, with a focus on recent discoveries that indicate that the rat hippocampus supports learning and decision-making behaviors via dynamic and smooth transitions in neural representation, internal processing state, and coupling with related brain structures.