A non-canonical striatopallidal Go pathway that supports motor control.

In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess axon collaterals within the globus pallidus (GPe) (bridging collaterals), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches in mice to dissect the roles of dSPN GPe collaterals in motor function.

Adult-born granule cells facilitate remapping of spatial and non-spatial representations in the dentate gyrus.

Adult-born granule cells (abGCs) have been implicated in memory discrimination through a neural computation known as pattern separation. Here, using in vivo Ca imaging, we examined how chronic ablation or acute chemogenetic silencing of abGCs affects the activity of mature granule cells (mGCs). In both cases, we observed altered remapping of mGCs.

Protocol for in vivo imaging and analysis of brainstem neuronal activity in the dorsal raphe nucleus of freely behaving mice.

In vivo brainstem imaging with miniature microscopy has been challenging due to surgical difficulty, high motion, and correlated activity between neurons. Here, we present a protocol for brainstem imaging in freely moving mice using the dorsal raphe nucleus as an example. We describe surgical procedures to inject a virus encoding GCaMP6m and securely implant a GRIN lens in the brainstem.

Single-cell activity and network properties of dorsal raphe nucleus serotonin neurons during emotionally salient behaviors.

The serotonin system modulates a wide variety of emotional behaviors and states, including reward processing, anxiety, and social interaction. To reveal the underlying patterns of neural activity, we visualized serotonergic neurons in the dorsal raphe nucleus (DRN) of mice using miniaturized microscopy during diverse emotional behaviors. We discovered ensembles of cells with highly correlated activity and found that DRN neurons are preferentially recruited by emotionally salient stimuli as opposed to neutral stimuli.

Parallel processing of sensory cue and spatial information in the dentate gyrus.

During exploration, animals form an internal map of an environment by combining information about landmarks and the animal's movement, a process that depends on the hippocampus. The dentate gyrus (DG) is the first stage of the hippocampal circuit where self-motion ("where") and sensory cue information ("what") are integrated, but it remains unknown how DG neurons encode this information during cognitive map formation. Using two-photon calcium imaging in mice running on a treadmill along with online cue manipulation, we identify robust sensory cue responses in DG granule cells.

A device for stereotaxic viral delivery into the brains of neonatal mice.

The increasing interest in manipulating neural circuits in developing brains has created a demand for reliable and accurate methods for delivering viruses to newborn mice. Here we describe a novel 3D-printed mouse neonatal stereotaxic adaptor for intracerebral viral injection that provides enhanced precision and reliability. Using this device, we injected mice with a -dependent hM4D-mCherry viral construct at postnatal day 1 (P1) and demonstrated selective expression in the striatal indirect pathway neurons on days P7, P11 and P25.

Contributions of adult neurogenesis to dentate gyrus network activity and computations.

Anatomical observations, theoretical work and lesion experiments have led to the idea that an important function of the dentate gyrus of the mammalian hippocampus is pattern separation, a neural computation that ensures new memories are encoded without interference from previously stored memories that share similar features. The dentate gyrus also exhibits a unique form of neural plasticity that results from the continuous integration of newly born excitatory granule cells, termed adult hippocampal neurogenesis. However, the manner in which adult neurogenesis contributes to dentate gyrus network activity and computations is incompletely understood.

Reinforcement Learning Recruits Somata and Apical Dendrites across Layers of Primary Sensory Cortex.

The mammalian brain can form associations between behaviorally relevant stimuli in an animal's environment. While such learning is thought to primarily involve high-order association cortex, even primary sensory areas receive long-range connections carrying information that could contribute to high-level representations. Here, we imaged layer 1 apical dendrites in the barrel cortex of mice performing a whisker-based operant behavior.

Effects of adult-generated granule cells on coordinated network activity in the dentate gyrus.

Throughout the adult life of most mammals, new neurons are continuously generated in the dentate gyrus of the hippocampal formation. Recent work has documented specific cognitive deficits after elimination of adult hippocampal neurogenesis in rodents, suggesting that these neurons may contribute to information processing in hippocampal circuits. Young adult-born neurons exhibit enhanced excitability and have altered capacity for synaptic plasticity in hippocampal slice preparations in vitro.

State-dependent alterations in hippocampal oscillations in serotonin 1A receptor-deficient mice.

Mice lacking the serotonin 1A receptor (5-HT(1A)R) show increased levels of anxiety-related behavior across multiple tests and background strains. Tissue-specific rescue experiments, lesion studies, and neurophysiological findings all point toward the hippocampus as a potential mediator of the phenotype. Serotonin, acting through 5-HT(1A)Rs, can suppress hippocampal theta-frequency oscillations, suggesting that theta oscillations might be increased in the knock-outs.

Global dendritic calcium spikes in mouse layer 5 low threshold spiking interneurones: implications for control of pyramidal cell bursting.

Interneuronal networks in neocortex underlie feedforward and feedback inhibition and control the temporal organization of pyramidal cell activity. We previously found that lower layer neocortical interneurones can reach action potential threshold in response to the stimulation of a single presynaptic cell. To better understand this phenomenon and the circuit roles of lower layer neocortical interneurones, we combined two-photon calcium imaging with whole cell recordings and anatomical reconstructions of low threshold spiking (LTS) interneurones from mouse neocortex.

Characterization of Caenorhabditis elegans homologs of the Down syndrome candidate gene DYRK1A.

The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1.