Voltage imaging reveals hippocampal inhibitory dynamics shaping pyramidal memory-encoding sequences.

Hippocampal spiking sequences encode and link behaviorally relevant information across time. How inhibition sculpts these sequences remains unclear. We performed longitudinal voltage imaging of CA1 parvalbumin- and somatostatin-expressing interneurons in mice performing an odor-cued working memory task.

Spontaneous movements and their relationship to neural activity fluctuate with latent engagement states.

Switching between cognitive states is a natural tendency, even for trained experts. To test how cognitive states impact neural activity and behavior, we measured cortex-wide neural activity during decision-making in mice. During disengagement, neural activity was more variable across trials and could be better explained by a linear encoding model.

An adaptable, reusable, and light implant for chronic Neuropixels probes.

Electrophysiology has proven invaluable to record neural activity, and the development of Neuropixels probes dramatically increased the number of recorded neurons. These probes are often implanted acutely, but acute recordings cannot be performed in freely moving animals and the recorded neurons cannot be tracked across days. To study key behaviors such as navigation, learning, and memory formation, the probes must be implanted chronically.

Large scale, simultaneous, chronic neural recordings from multiple brain areas.

Understanding how brain activity is related to animal behavior requires measuring multi-area interactions on multiple timescales. However, methods to perform chronic, simultaneous recordings of neural activity from many brain areas are lacking. Here, we introduce a novel approach for independent chronic probe implantation that enables flexible, simultaneous interrogation of neural activity from many brain regions during head restrained or freely moving behavior.

Spontaneous movements and their impact on neural activity fluctuate with latent engagement states.

Existing work demonstrates that animals alternate between engaged and disengaged states during perceptual decision-making. To understand the neural signature of these states, we performed cortex-wide measurements of neural activity in mice making auditory decisions. The trial-averaged magnitude of neural activity was similar in the two states.

Voltage imaging reveals that hippocampal interneurons tune memory-encoding pyramidal sequences.

Hippocampal spiking sequences encode and link behavioral information across time. How inhibition sculpts these sequences remains unknown. We performed longitudinal voltage imaging of CA1 parvalbumin- and somatostatin-expressing interneurons in mice during an odor-cued working memory task, before and after training.

Dysfunction of parvalbumin neurons in the cerebellar nuclei produces an action tremor.

Essential tremor is a common brain disorder affecting millions of people, yet the neuronal mechanisms underlying this prevalent disease remain elusive. Here, we showed that conditional deletion of synaptotagmin-2, the fastest Ca2+ sensor for synaptic neurotransmitter release, from parvalbumin neurons in mice caused an action tremor syndrome resembling the core symptom of essential tremor patients. Combining brain region-specific and cell type-specific genetic manipulation methods, we found that deletion of synaptotagmin-2 from excitatory parvalbumin-positive neurons in cerebellar nuclei was sufficient to generate an action tremor.

A central amygdala to zona incerta projection is required for acquisition and remote recall of conditioned fear memory.

The formation and retrieval of conditioned fear memories critically depend on the amygdala. Here we identify an inhibitory projection from somatostatin-positive neurons in the central amygdala to parvalbumin-positive neurons in the zona incerta that is required for both recent and remote fear memories. Thus, the amygdala inhibitory input to parvalbumin-positive neurons in the zona incerta, a nucleus not previously implicated in fear memory, is an essential component of the fear memory circuitry.