Neuropixels probes

How does a cat gracefully walk and suddenly freeze when spotting a mouse? In this talk, we look at how networks in the spinal cord generate movement. In particular, we address the fundamental yet poorly understood question of motor control: How can rhythmic movements, such as walking, be generated and stopped at any point in the cycle while posture is preserved? Since conventional models of spinal motor function rely on alternation between flexor and extensor modules, which are limited to just two phases, this question exposes the essential shortcoming of the conventional understanding: How ca

…We leveraged high-density Neuropixels probes to evaluate single-neuron acti

Hippocampus in mammals is hypothesized to support formation of episodic memory. Bedrock of this is based on the evidence of functional cell types related to immediate space, such as place cells. We aimed to test whether hippocampus, known for supporting spatial maps in physical environments, can localize the source of remote auditory signal and rewards associated with its spatial position. Given previous evidence for auditory sensitivity in the hippocampus [1-2], we recorded extracellular electrophysiological activity from auditory cortex and intermediate-ventral hippocampus simultaneously, us

Memory-related computations must occur across various brain states, each characterized by distinct oscillatory patterns. Theta oscillations in the hippocampal CA1 region are prominent during movement and are thought to organize network computations during active exploration, such as the virtual spatial paths formed by the sequential activity of CA1 spatial-tuning neurons, or 'place cells,' known as theta sequences. However, it remains unclear how theta supports memory during periods of immobility, when CA1 theta oscillations dissipate. To address this, we recorded laminar neural activity using

…is the recent development of the Neuropixels probe, which consists of a high-channel count Si shank with continuous, dense, programmable recording sites (~1000/cm). Neuropixels probes have transformed neurophysiological studies in rodent models by enabling recording from large populations of neurons anywh

Sharp-wave ripples (SWRs) are thought to play a crucial role in memory consolidation, learning, and the formation of long-term memories by facilitating the transfer of information from the hippocampus to neocortical networks. To understand the mechanisms governing SWRs, we have developed a closed-loop stimulation framework tailored for the real-time detection and suppression of SWRs, leveraging the ONIX electrophysiology acquisition system and BONSAI-RX acquisition software. As part of our Bonsai package, we developed a convolutional neural network (CNN) for detection of SWRs recorded with lam

The availability of high-density electrophysiology techniques is transforming systems neuroscience, enabling experimental labs to record activity from hundreds of neurons throughout the brain simultaneously. However, extracting single-cell activity from the resulting large datasets remains challenging, as various experimental conditions introduce sources of contaminating noise, and even optimized spike-sorting algorithms may produce false positive units. This requires labor-intensive manual evaluation of spike clusters.To address this challenge, we extended existing analyses and incorporated m

Sleep is an essential process observed throughout the animal kingdom, and it is important for memory consolidation. Coordinated neuronal activity occurs during sleep, characterized by distinct events across different sleep states. Non-rapid eye movement (NREM) sleep features slow oscillations, delta waves, thalamocortical spindles and hippocampal sharp waves-ripples, while REM sleep is dominated by hippocampal theta oscillations and ponto-geniculo-occipital (PGO) waves, or pontine waves (“P-waves”) in rodents. Even though their origin from mesopontine cholinergic and glutamatergic nuclei is kn

…cerebellar population activity with Neuropixels probes during locomotion in head-fixed mice, combined with high-speed 3D tracking of lim

Flexible integration of sensory information in a context-dependent manner is a key cognitive process required to generate appropriate behavior. An intriguing question, then, is how the same sensory stimulus can be interpreted differently according to context in order to generate different behavioral responses. We designed a task in which mice were trained to lick for reward in response to a brief single whisker stimulus if it was preceded by a brief Go-Tone presented one second before the whisker stimulus, but not if it was preceded by a NoGo-Tone. Optogenetic inactivation of primary whisker s

The striatum intricately regulates motor and cognitive functions through the dynamic interplay of dopamine (DA), acetylcholine (ACh), and intrinsic neuronal firing, bearing profound implications for disorders like Parkinson's. However, the interaction between striatal DA and ACh, and their collective impact on striatal neuron activity in health and disease, are not fully understood. This study aims to elucidate the complex interplay between ACh, DA, and neuronal activity in the striatum during sensory and motor events. Utilizing a specialized Delayed-Go reaching task for head-fixed mice, we re

The surround of the receptive field (RF) has been traditionally considered to modulate neural responses within the RF. However, recent studies have challenged this conventional understanding, showing elevated firing rates in primary visual cortex (V1) in response to stimuli presented in the surround, even in the absence of direct visual input within the classical RF. While the responses in absence of visual input have been interpreted as a prediction of the occluded content, we alternatively propose that the increased responses to the surround stimulation are the representation of a uniform ac

…electrophysiological recordings with Neuropixels probes in awake, behaving mice in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively). We used the MitoPark mouse, a genetic model of PD, to in

Humans and other animals require flexibility to make decisions appropriate for an ever-changing environment. The way mammalian brains achieve flexible decision making is not fully understood. The probabilistic reversal learning (PRL) task is a powerful tool used to assess behavioral flexibility and how positive and negative feedbacks influence decision making, both in healthy subjects and in patients with a wide range of neurological conditions like Autistic Spectrum Disorder and Schizophrenia, as well as animal models. We trained C57BL/6 mice on PRL and conducted high-density single unit reco

…We used multiple Neuropixels probes to simultaneously record population activity across cortical and subcortical regions during a goal-directed reaching task in mice. Task-related population activity followed dominant latent dynamics across all rec

Medial septal (MS) glutamatergic neurons expressing type 2 vesicular glutamate transporter (VGluT2) are active during theta oscillation and locomotor activity. Optogenetic activation of these neurons at theta frequencies (4-12 Hz) entrains hippocampal theta oscillation and sustains locomotion outlasting the stimulus duration. However, the specific cellular and circuit mechanisms responsible for initiating and sustaining MS VGluT2-driven persistent locomotion and associated hippocampal theta oscillations remain unclear. To address these questions, we optogenetically targeted glutamatergic neuro

The integration of sensory inputs from different senses is a crucial aspect of sensory perception and behavioral decisions. Whether such multisensory integration occurs at specific stages of neural processing remains unclear. Two brain regions, the anterolateral motor cortex (ALM) and the superior colliculus (SC) are important parts of a cortico-subcortical loop that transforms multisensory inputs into behavioral decisions. To study the role of these areas in multisensory integration and decision-making, we trained mice in a multisensory discrimination task, where animals had to integrate visu

Over the past decade, considerable research has delved into the Retrosplenial Cortex's (RSC) critical function in spatial navigation, employing allocentric and egocentric frames of reference to interact with its surroundings. Andy Alexander's 2018 study on Egocentric Boundary Vector Cells (EBVCs) in the RSC in an open-field arena marked a significant advancement in our understanding. Building on this foundation, our study extends the investigation into EBVCs' roles in navigation within an open field context and in a dynamic egocentric task—specifically, a rat pursuing a bait within the same en

Social cognition is believed to contribute to the collective success of groups. To learn from others, individuals must form representations of their own and conspecifics’ actions and outcomes, integrating this information to enhance their understanding of the environment. Neurons in the frontal cortex of socially interacting mice represent various aspects of conspecific behavior, including fear, pain, competition, and social hierarchy. However, whether these neural circuits are involved in observational reinforcement learning during goal-directed tasks remains to be determined. To investigate

Recognizing and remembering social conspecifics is crucial for the survival of an organism, but it remains unclear how this information is represented in the brain. Previously, we identified populations of basolateral amygdala (BLA) neurons in the freely-moving rat that were highly tuned to distinct naturalistic stimuli such as male or female conspecifics and food. These neuronal populations showed stable reactivation across multiple presentations of stimuli in the same environment. To understand whether experience can modify this social representation, we recorded from large populations of ne

…of neuronal data acquired using Neuropixels probes. Each of these tools, however, focus on a part of the entire pipeline from raw data to spike- and event times. For example, SpikeInterface is an incredibly useful Python module for pre-processing and spike sorting of individual recordings. However, there are more steps in between raw data and spikes, such as synchronization of spike times between probes and histological reconstruction of probe insertions. Large collaborations, like the International Brain Laboratory (IBL), hav

How does the hippocampus know when to store a new memory?We hypothesize that when animals transition into a novel environment,a transient small increase in Dentate Gyrus(DG) activity triggers downstream circuits to establish new neuronal representations.To empirically test this hypothesis,we focus on understanding how neuronal population activity in hippocampal subregions responds to transitions from a familiar(F) to a novel(N) environment. We use an immersive virtual reality setup adapted for rodent head-fixed navigation (n= 6mice).After five consecutive daily training sessions in the familia

…recorded using Cambridge NeuroTech and Neuropixels probes. Neurons exhibited

Sharp-wave ripples (SWRs) are thought to play a crucial role in memory consolidation, learning, and the formation of long-term memories by facilitating the transfer of information from the hippocampus to neocortical networks. To understand the mechanisms governing SWRs, we have developed a closed-loop stimulation framework tailored for the real-time detection and suppression of SWRs, leveraging the ONIX electrophysiology acquisition system and BONSAI-RX acquisition software. As part of our Bonsai package, we developed a convolutional neural network (CNN) for detection of SWRs recorded with lam