Biology subjects

Lehr, A. B.

Publications and source records attributed to Lehr, A. B..

3 recordsLinked to original sources

bioRxiv2023

Competition and Cooperation of Assembly Sequences in Recurrent Neural Networks

Neural activity sequences are ubiquitous in the brain and play pivotal roles in functions such as long-term memory formation and motor control. While conditions for storing and reactivating individual sequences have been thoroughly characterized, it remains unclear how multiple sequences may interact when activated simultaneously in recurrent neural networks. This question is especially relevant for weak sequences, comprised of fewer neurons, competing against strong sequences. Using a non-linear rate model with discrete, pre-configured assemblies, we demonstrate that weak sequences can compensate for their competitive disadvantage either by increasing excitatory connections between subsequent assemblies or by cooperating with other co-active sequences. Further, our model suggests that such cooperation can negatively affect sequence speed unless subsequently active assemblies are paired. Our analysis, validated by an analytically tractable linear approximation, characterizes the conditions for successful sequence progression in isolated, competing, and cooperating sequences, and identifies the distinct contributions of recurrent and feed-forward projections. This proof-of-principle study shows how even disadvantaged sequences can be prioritized for reactivation, a process which has recently been implicated in hippocampal memory processing.

neuroscience↗

bioRxiv2023

Sparse clustered inhibition projects sequential activity onto unique neural subspaces

Neural activity in the brain traces sequential trajectories on low dimensional subspaces. For flexible behavior, these neural subspaces must be manipulated and reoriented within short timescales of tens of milliseconds. Using mathematical analysis and simulation of a recurrently connected neural circuit for sequence generation, we report that incorporating a subtype of interneurons that provides spatially heterogeneous inhibition enables the projection of sequential activity onto task- or context-specific neural subspaces. Depending on the sparsity of inhibitory projections, neural subspaces could be arbitrarily rotated, without altering the key aspects of sequence generation. Thus, we propose a circuit motif by which inhibitory interneurons can enable flexible switching between neural subspaces on a fast timescale of milliseconds, controlled by top down signals.

neuroscience↗

bioRxiv2022

Silencing hippocampal CA2 reduces behavioral flexibility in spatial learning

The hippocampus is a key structure involved in learning and remembering spatial information. However the extent to which hippocampal region CA2 is involved in these processes remains unclear. Here we show that chronically silencing dorsal CA2 impairs reversal learning in the Morris water maze. After platform relocation, CA2-silenced mice spent more time in the vicinity of the old platform location and less time in the new target quadrant. Accordingly, behavioral strategy analysis revealed increased perseverance in navigating to the old location during the first day and an increased use of non-spatial strategies during the second day of reversal learning. Confirming previous indirect indications, these results demonstrate that CA2 is recruited when mice must flexibly adapt their behavior as task contingencies change. We discuss how these findings can be explained by recent theories of CA2 function and outline testable predictions to understand the underlying neural mechanisms. Demonstrating a direct involvement of CA2 in spatial learning, this work lends further support to the notion that CA2 plays a fundamental role in hippocampal information processing.

neuroscience↗