The auditory midbrain mediates tactile vibration sensing.

Vibrations are ubiquitous in nature, shaping behavior across the animal kingdom. For mammals, mechanical vibrations acting on the body are detected by mechanoreceptors of the skin and deep tissues and processed by the somatosensory system, while sound waves traveling through air are captured by the cochlea and encoded in the auditory system. Here, we report that mechanical vibrations detected by the body's Pacinian corpuscle neurons, which are distinguished by their ability to entrain to high-frequency (40-1,000 Hz) environmental vibrations, are prominently encoded by neurons in the lateral cortex of the inferior colliculus (LCIC) of the midbrain.

C-LTMRs evoke wet dog shakes via the spinoparabrachial pathway.

Many hairy mammals perform rapid oscillations of their body, called wet dog shakes, to remove water and irritants from their back hairy skin. The somatosensory mechanisms that underlie this behavior are unclear. We report that Piezo2-dependent mechanosensation mediates wet dog shakes evoked by water or oil droplets applied to back hairy skin of mice.

C-LTMRs mediate wet dog shakes via the spinoparabrachial pathway.

Mammals perform rapid oscillations of their body- "wet dog shakes" -to remove water and irritants from their back hairy skin. The somatosensory mechanisms underlying this stereotypical behavior are unknown. We report that Piezo2-dependent mechanosensation mediates wet dog shakes evoked by water or oil droplets applied to hairy skin of mice.

The auditory midbrain mediates tactile vibration sensing.

Vibrations are ubiquitous in nature, shaping behavior across the animal kingdom. For mammals, mechanical vibrations acting on the body are detected by mechanoreceptors of the skin and deep tissues and processed by the somatosensory system, while sound waves traveling through air are captured by the cochlea and encoded in the auditory system. Here, we report that mechanical vibrations detected by the body's Pacinian corpuscle neurons, which are unique in their ability to entrain to high frequency (40-1000 Hz) environmental vibrations, are prominently encoded by neurons in the lateral cortex of the inferior colliculus (LCIC) of the midbrain.

The developmental timing of spinal touch processing alterations predicts behavioral changes in genetic mouse models of autism spectrum disorders.

Altered somatosensory reactivity is frequently observed among individuals with autism spectrum disorders (ASDs). Here, we report that although multiple mouse models of ASD exhibit aberrant somatosensory behaviors in adulthood, some models exhibit altered tactile reactivity as early as embryonic development, whereas in others, altered reactivity emerges later in life. Additionally, tactile overreactivity during neonatal development is associated with anxiety-like behaviors and social behavior deficits in adulthood, whereas tactile overreactivity that emerges later in life is not.

Activity-dependent development of the body's touch receptors.

We report a role for activity in the development of the primary sensory neurons that detect touch. Genetic deletion of Piezo2, the principal mechanosensitive ion channel in somatosensory neurons, caused profound changes in the formation of mechanosensory end organ structures and altered somatosensory neuron central targeting. Single cell RNA sequencing of conditional mutants revealed changes in gene expression in the sensory neurons activated by light mechanical forces, whereas other neuronal classes were less affected.

Coding of self and environment by Pacinian neurons in freely moving animals.

Pacinian corpuscle neurons are specialized low-threshold mechanoreceptors (LTMRs) that are tuned to detect high-frequency vibration (~40-2000 Hz), however it is unclear how Pacinians and other LTMRs encode mechanical forces encountered during naturalistic behavior. Here, we developed methods to record LTMRs in awake, freely moving mice. We find that Pacinians, but not other LTMRs, encode subtle vibrations of surfaces encountered by the animal, including low-amplitude vibrations initiated over two meters away.

Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch.

Across mammalian skin, structurally complex and diverse mechanosensory end organs respond to mechanical stimuli and enable our perception of dynamic, light touch. How forces act on morphologically dissimilar mechanosensory end organs of the skin to gate the requisite mechanotransduction channel Piezo2 and excite mechanosensory neurons is not understood. Here, we report high-resolution reconstructions of the hair follicle lanceolate complex, Meissner corpuscle, and Pacinian corpuscle and the subcellular distribution of Piezo2 within them.

The developmental timing of spinal touch processing alterations and its relation to ASD-associated behaviors in mouse models.

Altered somatosensory reactivity is frequently observed among individuals with autism spectrum disorders (ASDs). Here, we report that while multiple mouse models of ASD exhibit aberrant somatosensory behaviors in adulthood, some models exhibit altered tactile reactivity as early as embryonic development, while in others, altered reactivity emerges later in life. Additionally, tactile over-reactivity during neonatal development is associated with anxiety-like behaviors and social interaction deficits in adulthood, whereas tactile over-reactivity that emerges later in life is not.

Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch.

Specialized mechanosensory end organs within mammalian skin-hair follicle-associated lanceolate complexes, Meissner corpuscles, and Pacinian corpuscles-enable our perception of light, dynamic touch . In each of these end organs, fast-conducting mechanically sensitive neurons, called Aβ low-threshold mechanoreceptors (Aβ LTMRs), associate with resident glial cells, known as terminal Schwann cells (TSCs) or lamellar cells, to form complex axon ending structures. Lanceolate-forming and corpuscle-innervating Aβ LTMRs share a low threshold for mechanical activation, a rapidly adapting (RA) response to force indentation, and high sensitivity to dynamic stimuli .

The encoding of touch by somatotopically aligned dorsal column subdivisions.

The somatosensory system decodes a range of tactile stimuli to generate a coherent sense of touch. Discriminative touch of the body depends on signals conveyed from peripheral mechanoreceptors to the brain through the spinal cord dorsal column and its brainstem target, the dorsal column nuclei (DCN). Models of somatosensation emphasize that fast-conducting low-threshold mechanoreceptors (LTMRs) innervating the skin drive the DCN.

Introduction of synaptotagmin 7 promotes facilitation at the climbing fiber to Purkinje cell synapse.

Synaptotagmin 7 (Syt7) is a high-affinity calcium sensor that is implicated in multiple aspects of synaptic transmission. Here, we study the influence of Syt7 on the climbing fiber (CF) to Purkinje cell (PC) synapse. We find that small facilitation and prominent calcium-dependent recovery from depression at this synapse do not rely on Syt7 and that Syt7 is not normally present in CFs.

Cerebellar and vestibular nuclear synapses in the inferior olive have distinct release kinetics and neurotransmitters.

The inferior olive (IO) is composed of electrically-coupled neurons that make climbing fiber synapses onto Purkinje cells. Neurons in different IO subnuclei are inhibited by synapses with wide ranging release kinetics. Inhibition can be exclusively synchronous, asynchronous, or a mixture of both.

Influence of ocular dominance columns and patchy callosal connections on binocularity in lateral striate cortex: Long Evans versus albino rats.

In albino rats, it has been reported that lateral striate cortex (V1) is highly binocular, and that input from the ipsilateral eye to this region comes through the callosum. In contrast, in Long Evans rats, this region is nearly exclusively dominated by the contralateral eye even though it is richly innervated by the callosum (Laing, Turecek, Takahata, & Olavarria, 2015). We hypothesized that the inability of callosal connections to relay ipsilateral eye input to lateral V1 in Long Evans rats is a consequence of the existence of ocular dominance columns (ODCs), and of callosal patches in register with ipsilateral ODCs in the binocular region of V1 (Laing et al.

The Role of Ca2.1 Channel Facilitation in Synaptic Facilitation.

Activation of Ca2.1 voltage-gated calcium channels is facilitated by preceding calcium entry. Such self-modulatory facilitation is thought to contribute to synaptic facilitation.

Neuronal Regulation of Fast Synaptotagmin Isoforms Controls the Relative Contributions of Synchronous and Asynchronous Release.

Neurotransmitter release can be synchronous and occur within milliseconds of action potential invasion, or asynchronous and persist for tens of milliseconds. The molecular determinants of release kinetics remain poorly understood. It has been hypothesized that asynchronous release dominates when fast Synaptotagmin isoforms are far from calcium channels or when specialized sensors, such as Synaptotagmin 7, are abundant.

Synaptotagmin 7 Mediates Both Facilitation and Asynchronous Release at Granule Cell Synapses.

When an action potential invades a presynaptic terminal it evokes large, brief Ca signals that trigger vesicle fusion within milliseconds that is followed by a small residual Ca (Ca) signal. At many synapses Ca produces synaptic facilitation that lasts up to hundreds of milliseconds and, although less common, Ca can also evoke asynchronous release (AR) that persists for tens of milliseconds. The properties of facilitation and AR are very different, which suggests that they are mediated by distinct mechanisms.

Synaptotagmin 7 confers frequency invariance onto specialized depressing synapses.

At most synapses in the brain, short-term plasticity dynamically modulates synaptic strength. Rapid frequency-dependent changes in synaptic strength have key roles in sensory adaptation, gain control and many other neural computations. However, some auditory, vestibular and cerebellar synapses maintain constant strength over a wide range of firing frequencies, and as a result efficiently encode firing rates.

Synaptic Specializations Support Frequency-Independent Purkinje Cell Output from the Cerebellar Cortex.

The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells (PCs). Here, we characterize the properties of the PC-DCN synapse in juvenile and adult mice and find that prolonged high-frequency stimulation leads to steady-state responses that become increasingly frequency independent within the physiological firing range of PCs in older animals, resulting in a linear relationship between charge transfer and activation frequency. We used a low-affinity antagonist to show that GABA-receptor saturation occurs at this synapse but does not underlie frequency-invariant transmission.

Electrical Coupling and Synchronized Subthreshold Oscillations in the Inferior Olive of the Rhesus Macaque.

Unlabelled: Inferior olive (IO) neurons are critical for motor coordination and exhibit oscillations in membrane potential that are subthreshold for spiking. The prevalence, coherence, and continuity of those subthreshold oscillations (STOs) depend upon resonant interactions between neighboring neurons supported by electrical coupling. Many studies of the olivocerebellar system in rodents, in which STOs were related to tremor, whisking, and licking, fueled a debate over whether IO STOs were relevant for primates whose repertoire of movement is generally less periodic.

The calcium sensor synaptotagmin 7 is required for synaptic facilitation.

It has been known for more than 70 years that synaptic strength is dynamically regulated in a use-dependent manner. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement in which each subsequent action potential evokes greater neurotransmitter release. Facilitation can enhance neurotransmitter release considerably and can profoundly influence information transfer across synapses, but the underlying mechanism remains a mystery.

Identification of Eye-Specific Domains and Their Relation to Callosal Connections in Primary Visual Cortex of Long Evans Rats.

Ocular dominance columns (ODCs) exist in many primates and carnivores, but it is believed that they do not exist in rodents. Using a combination of transneuronal tracing, in situ hybridization for Zif268 and electrophysiological recordings, we show that inputs from both eyes are largely segregated in the binocular region of V1 in Long Evans rats. We also show that, interposed between this binocular region and the lateral border of V1, there lies a strip of cortex that is strongly dominated by the contralateral eye.

RNA interference of GluN1 inhibits neuronal rhythmogenesis in the adult inferior olive.

RNA interference (RNAi) to knockdown N-methyl-D-aspartate receptor (NMDAR) function is being investigated to address disorders associated with pathological brain rhythms. A motivating finding has been that pharmacological block of NMDARs inhibited oscillations in neuronal membrane potential that entrain rhythmic bursts of action potentials. To determine whether transient effects of NMDAR antagonist drugs to inhibit neuronal rhythmicity can be stably induced with genetic specificity, we examined the effects of RNAi of GluN1 protein on the subthreshold oscillations (STOs) of neurons in the inferior olive (IO), a pacemaking nucleus necessary for motor and cognitive timing.

NMDA receptor activation strengthens weak electrical coupling in mammalian brain.

Electrical synapses are formed by gap junctions and permit electrical coupling, which shapes the synchrony of neuronal ensembles. Here, we provide a direct demonstration of receptor-mediated strengthening of electrical coupling in mammalian brain. Electrical coupling in the inferior olive of rats was strengthened by activation of NMDA-type glutamate receptors (NMDARs), which were found at synaptic loci and at extrasynaptic loci 20-100 nm proximal to gap junctions.