Court Alan Hull

Journal Article Proc Natl Acad Sci U S A · August 20, 2024 Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. Individuals with ASTN2 mutations exhibit neurodevelopmental d ... Full text Link to item Cite

Specialized connectivity of molecular layer interneuron subtypes leads to disinhibition and synchronous inhibition of cerebellar Purkinje cells.

Journal Article Neuron · July 17, 2024 Molecular layer interneurons (MLIs) account for approximately 80% of the inhibitory interneurons in the cerebellar cortex and are vital to cerebellar processing. MLIs are thought to primarily inhibit Purkinje cells (PCs) and suppress the plasticity of syna ... Full text Link to item Cite

DART.2: bidirectional synaptic pharmacology with thousandfold cellular specificity.

Journal Article Nat Methods · July 2024 Precision pharmacology aims to manipulate specific cellular interactions within complex tissues. In this pursuit, we introduce DART.2 (drug acutely restricted by tethering), a second-generation cell-specific pharmacology technology. The core advance is opt ... Full text Link to item Cite

A deep-learning strategy to identify cell types across species from high-density extracellular recordings.

Journal Article bioRxiv · May 5, 2024 High-density probes allow electrophysiological recordings from many neurons simultaneously across entire brain circuits but don't reveal cell type. Here, we develop a strategy to identify cell types from extracellular recordings in awake animals, revealing ... Full text Link to item Cite

Local synaptic inhibition mediates cerebellar granule cell pattern separation and enables learned sensorimotor associations.

Journal Article Nat Neurosci · April 2024 The cerebellar cortex has a key role in generating predictive sensorimotor associations. To do so, the granule cell layer is thought to establish unique sensorimotor representations for learning. However, how this is achieved and how granule cell populatio ... Full text Link to item Cite

Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties.

Journal Article bioRxiv · February 18, 2024 Astrotactin 2 (ASTN2) is a transmembrane neuronal protein highly expressed in the cerebellum that functions in receptor trafficking and modulates cerebellar Purkinje cell (PC) synaptic activity. We recently reported a family with a paternally inherited int ... Full text Link to item Cite

Cerebellar circuits for disinhibition and synchronous inhibition.

Journal Article bioRxiv · September 15, 2023 The cerebellar cortex contributes to diverse behaviors by transforming mossy fiber inputs into predictions in the form of Purkinje cell (PC) outputs, and then refining those predictions1. Molecular layer interneurons (MLIs) account for approximately 80% of ... Full text Link to item Cite

The Cerebellar Cortex.

Journal Article Annu Rev Neurosci · July 8, 2022 The cerebellar cortex is an important system for relating neural circuits and learning. Its promise reflects the longstanding idea that it contains simple, repeated circuit modules with only a few cell types and a single plasticity mechanism that mediates ... Full text Link to item Cite

Local synaptic inhibition mediates cerebellar granule cell pattern separation necessary for learned sensorimotor associations

Preprint · May 21, 2022 Full text Cite

Designing Behavioral Tasks for Cerebellar Functional Analysis in the Mouse

Chapter · January 1, 2022 Cerebellar research is rapidly expanding beyond the study of traditional cerebellar-dependent motor behaviors. As it has become widely recognized that the cerebellum contributes to a range of sensorimotor behaviors that also include the social and cognitiv ... Full text Cite

Acetylcholine Modulates Cerebellar Granule Cell Spiking by Regulating the Balance of Synaptic Excitation and Inhibition.

Journal Article J Neurosci · April 1, 2020 Sensorimotor integration in the cerebellum is essential for refining motor output, and the first stage of this processing occurs in the granule cell layer. Recent evidence suggests that granule cell layer synaptic integration can be contextually modified, ... Full text Open Access Link to item Cite

Prediction signals in the cerebellum: beyond supervised motor learning.

Journal Article Elife · March 30, 2020 While classical views of cerebellar learning have suggested that this structure predominantly operates according to an error-based supervised learning rule to refine movements, emerging evidence suggests that the cerebellum may also harness a wider range o ... Full text Link to item Cite

Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum.

Journal Article Elife · September 11, 2019 Classical models of cerebellar learning posit that climbing fibers operate according to a supervised learning rule to instruct changes in motor output by signaling the occurrence of movement errors. However, cerebellar output is also associated with non-mo ... Full text Link to item Cite

Serotonin regulates dynamics of cerebellar granule cell activity by modulating tonic inhibition.

Journal Article J Neurophysiol · January 1, 2019 Understanding how afferent information is integrated by cortical structures requires identifying the factors shaping excitation and inhibition within their input layers. The input layer of the cerebellar cortex integrates diverse sensorimotor information t ... Full text Link to item Cite

Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum

Journal Article · 2019 Classical models of cerebellar learning posit that climbing fibers operate according to a supervised learning rule to instruct changes in motor output by signaling the occurrence of movement errors. However, cerebellar output is also associated with non-mo ... Full text Cite

Acetylcholine modulates cerebellar granule cell spiking by regulating the balance of synaptic excitation and inhibition

Journal Article · 2019 Sensorimotor integration in the cerebellum is essential for refining motor output, and the first stage of this processing occurs in the granule cell layer. Recent evidence suggests that granule cell layer synaptic integration can be contextually modified, ... Full text Cite

ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins.

Journal Article Proc Natl Acad Sci U S A · October 9, 2018 Surface protein dynamics dictate synaptic connectivity and function in neuronal circuits. ASTN2, a gene disrupted by copy number variations (CNVs) in neurodevelopmental disorders, including autism spectrum, was previously shown to regulate the surface expr ... Full text Link to item Cite

Coordinated cerebellar climbing fiber activity signals learned sensorimotor predictions.

Journal Article Nat Neurosci · October 2018 Featured Publication The prevailing model of cerebellar learning states that climbing fibers (CFs) are both driven by, and serve to correct, erroneous motor output. However, this model is grounded largely in studies of behaviors that utilize hardwired neural pathways to link s ... Full text Link to item Cite

The cerebellum influences vocal timing.

Journal Article Elife · August 28, 2018 A circuit pathway from the cerebellum to the basal ganglia contributes to vocal learning in songbirds. ... Full text Link to item Cite

A subcortical circuit linking the cerebellum to the basal ganglia engaged in vocal learning

Journal Article eLife · July 25, 2018 Speech is a complex sensorimotor skill, and vocal learning involves both the basal ganglia and the cerebellum. These subcortical structures interact indirectly through their respective loops with thalamo-cortical and brainstem networks, and directl ... Full text Cite

Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties.

Specialized connectivity of molecular layer interneuron subtypes leads to disinhibition and synchronous inhibition of cerebellar Purkinje cells.

DART.2: bidirectional synaptic pharmacology with thousandfold cellular specificity.

A deep-learning strategy to identify cell types across species from high-density extracellular recordings.

Local synaptic inhibition mediates cerebellar granule cell pattern separation and enables learned sensorimotor associations.

Mice lacking Astn2 have ASD-like behaviors and altered cerebellar circuit properties.

Cerebellar circuits for disinhibition and synchronous inhibition.

The Cerebellar Cortex.

Local synaptic inhibition mediates cerebellar granule cell pattern separation necessary for learned sensorimotor associations

Preprint · May 21, 2022 Full text Cite

Designing Behavioral Tasks for Cerebellar Functional Analysis in the Mouse

Acetylcholine Modulates Cerebellar Granule Cell Spiking by Regulating the Balance of Synaptic Excitation and Inhibition.

Prediction signals in the cerebellum: beyond supervised motor learning.

Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum.

Serotonin regulates dynamics of cerebellar granule cell activity by modulating tonic inhibition.

Classical conditioning drives learned reward prediction signals in climbing fibers across the lateral cerebellum

Acetylcholine modulates cerebellar granule cell spiking by regulating the balance of synaptic excitation and inhibition

ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins.

Coordinated cerebellar climbing fiber activity signals learned sensorimotor predictions.

The cerebellum influences vocal timing.

Journal Article Elife · August 28, 2018 A circuit pathway from the cerebellum to the basal ganglia contributes to vocal learning in songbirds. ... Full text Link to item Cite

A subcortical circuit linking the cerebellum to the basal ganglia engaged in vocal learning

Cellular and Synaptic Properties of Local Inhibitory Circuits.

Journal Article Cold Spring Harb Protoc · May 1, 2017 Inhibitory interneurons play a key role in sculpting the information processed by neural circuits. Despite the wide range of physiologically and morphologically distinct types of interneurons that have been identified, common principles have emerged that h ... Full text Link to item Cite

Measuring Feedforward Inhibition and Its Impact on Local Circuit Function.

Journal Article Cold Spring Harb Protoc · May 1, 2017 This protocol describes a series of approaches to measure feedforward inhibition in acute brain slices from the cerebellar cortex. Using whole-cell voltage and current clamp recordings from Purkinje cells in conjunction with electrical stimulation of the p ... Full text Link to item Cite

Active Dendrites and Differential Distribution of Calcium Channels Enable Functional Compartmentalization of Golgi Cells.

Journal Article J Neurosci · November 25, 2015 UNLABELLED: Interneurons are essential to controlling excitability, timing, and synaptic integration in neuronal networks. Golgi cells (GoCs) serve these roles at the input layer of the cerebellar cortex by releasing GABA to inhibit granule cells (grcs). G ... Full text Link to item Cite

Hyperpolarization induces a long-term increase in the spontaneous firing rate of cerebellar Golgi cells.

Journal Article J Neurosci · April 3, 2013 Golgi cells (GoCs) are inhibitory interneurons that influence the cerebellar cortical response to sensory input by regulating the excitability of the granule cell layer. While GoC inhibition is essential for normal motor coordination, little is known about ... Full text Link to item Cite

Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice.

Journal Article Nature · August 30, 2012 Autism spectrum disorders (ASDs) are highly prevalent neurodevelopmental disorders, but the underlying pathogenesis remains poorly understood. Recent studies have implicated the cerebellum in these disorders, with post-mortem studies in ASD patients showin ... Full text Link to item Cite

Identification of an inhibitory circuit that regulates cerebellar Golgi cell activity.

Journal Article Neuron · January 12, 2012 Here we provide evidence that revises the inhibitory circuit diagram of the cerebellar cortex. It was previously thought that Golgi cells, interneurons that are the sole source of inhibition onto granule cells, were exclusively coupled via gap junctions. M ... Full text Link to item Cite

Multiple clusters of release sites formed by individual thalamic afferents onto cortical interneurons ensure reliable transmission.

Journal Article Neuron · July 14, 2011 Thalamic afferents supply the cortex with sensory information by contacting both excitatory neurons and inhibitory interneurons. Interestingly, thalamic contacts with interneurons constitute such a powerful synapse that even one afferent can fire interneur ... Full text Link to item Cite

Postsynaptic mechanisms govern the differential excitation of cortical neurons by thalamic inputs.

Journal Article J Neurosci · July 15, 2009 Thalamocortical (TC) afferents relay sensory input to the cortex by making synapses onto both excitatory regular-spiking principal cells (RS cells) and inhibitory fast-spiking interneurons (FS cells). This divergence plays a crucial role in coordinating ex ... Full text Link to item Cite

Neocortical disynaptic inhibition requires somatodendritic integration in interneurons.

Journal Article J Neurosci · July 15, 2009 In his theory of functional polarity, Ramon y Cajal first identified the soma and dendrites as the principal recipient compartments of a neuron and the axon as its main output structure. Despite notable exceptions in other parts of the nervous system (Scho ... Full text Link to item Cite

It's about time for thalamocortical circuits.

Journal Article Nat Neurosci · April 2007 The timing of thalamocortical excitation and inhibition is critical to local microcircuits. Two new papers shed light on the development and performance of a somatosensory microcircuit that regulates the integration of thalamic inputs. ... Full text Link to item Cite

Diurnal changes in exocytosis and the number of synaptic ribbons at active zones of an ON-type bipolar cell terminal.

Journal Article J Neurophysiol · October 2006 The number and morphology of synaptic ribbons at photoreceptor and bipolar cell terminals has been reported to change on a circadian cycle. Here we sought to determine whether this phenomenon exists at goldfish Mb-type bipolar cell terminals with the aim o ... Full text Link to item Cite

GABA transporters regulate a standing GABAC receptor-mediated current at a retinal presynaptic terminal.

Journal Article J Neurosci · June 28, 2006 At the axon terminal of goldfish retinal bipolar cells, GABA(C) receptors have been shown to mediate inhibitory reciprocal synaptic currents. Here, we demonstrate a novel standing GABAergic current mediated exclusively by GABA(C) receptors. Selective inhib ... Full text Link to item Cite

Long-term plasticity mediated by mGluR1 at a retinal reciprocal synapse.

Journal Article Neuron · May 5, 2005 The flow of information across the retina is controlled by reciprocal synapses between bipolar cell terminals and amacrine cells. However, the synaptic delays and properties of plasticity at these synapses are not known. Here we report that glutamate relea ... Full text Link to item Cite

Fast endocytosis is inhibited by GABA-mediated chloride influx at a presynaptic terminal.

Journal Article Neuron · October 28, 2004 Although multiple kinetic components of synaptic vesicle endocytosis have been identified, it has remained unclear whether neurons can differentially modulate these components. Using membrane capacitance measurements from isolated goldfish bipolar cell ter ... Full text Link to item Cite

Synaptic cleft acidification and modulation of short-term depression by exocytosed protons in retinal bipolar cells.

Journal Article J Neurosci · December 10, 2003 The release of vesicular protons during exocytosis causes a feedback inhibition of Ca2+ channels in photoreceptor terminals; however, the effect of this inhibition on subsequent exocytosis has not been studied. Here we show that a similar L-type Ca2+ chann ... Full text Link to item Cite

Synaptic activation of presynaptic glutamate transporter currents in nerve terminals.

Journal Article J Neurosci · June 15, 2003 Glutamate uptake by high-affinity transporters is responsible for limiting the activation of postsynaptic receptors and maintaining low levels of ambient glutamate. The reuptake process generates membrane currents, which can be activated by synaptically re ... Full text Link to item Cite

Okadaic acid disrupts synaptic vesicle trafficking in a ribbon-type synapse.

Journal Article J Neurochem · September 2002 Protein phosphorylation plays an essential role in regulating synaptic transmission and plasticity. However, regulation of vesicle trafficking towards and away from the plasma membrane is poorly understood. Furthermore, the extent to which phosphorylation ... Full text Link to item Cite

Synaptic Transmission

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