Sensory neuron PIEZO1 deletion inhibits dynamic light touch sensitivity in uninjured mice, prevents neuropathic light touch hypersensitivity, and drives compensatory changes in dorsal root ganglia.

Mechanotransduction is vital for sensing various mechanical stimuli, including blunt force and dynamic light touch. The sensation of a punctate mechanical force is very different from that of a brush swept across the skin, yet both involve mechanical stimulation of the skin and embedded sensory afferent endings. However, the sensory neuron mechanisms contributing to punctate vs light touch somatosensation, and how they might become dysregulated in nerve injury to cause pain, remain unclear.

Fear conditioning modulates the intrinsic excitability of ventral hippocampal CA1 neurons in male rats.

The hippocampus has a known role in learning and memory, with the ventral subregion supporting many learning tasks involving affective responding, including fear conditioning. Altered neuronal intrinsic excitability reflects experience-dependent plasticity that supports learning-related behavioral changes. Such changes have previously been observed in the dorsal hippocampus following fear conditioning, but little work has examined the effect of fear conditioning on ventral hippocampal intrinsic plasticity.

Schwann cell release of p11 induces sensory neuron hyperactivity in Fabry disease.

Patients with Fabry disease suffer from chronic debilitating pain and peripheral sensory neuropathy with minimal treatment options, but the cellular drivers of this pain are unknown. Here, we propose a novel mechanism by which altered signaling between Schwann cells and sensory neurons underlies the peripheral sensory nerve dysfunction we observe in a genetic rat model of Fabry disease. Using and electrophysiological recordings, we demonstrate that Fabry rat sensory neurons exhibit pronounced hyperexcitability.

Gut microbiota and metabolites drive chronic sickle cell disease pain.

Pain is a debilitating symptom and leading reason for hospitalization of individuals with sickle cell disease. Chronic sickle cell pain is poorly managed because the biological basis is not fully understood. Using transgenic sickle cell mice and fecal material transplant, we determined that the gut microbiome drives persistent sickle cell pain.

Peripheral transient receptor potential vanilloid type 4 hypersensitivity contributes to chronic sickle cell disease pain.

Debilitating pain affects the lives of patients with sickle cell disease (SCD). Current pain treatment for patients with SCD fail to completely resolve acute or chronic SCD pain. Previous research indicates that the cation channel transient receptor potential vanilloid type 4 (TRPV4) mediates peripheral hypersensitivity in various inflammatory and neuropathic pain conditions that may share similar pathophysiology with SCD, but this channel's role in chronic SCD pain remains unknown.

Apoaequorin differentially modulates fear memory in adult and aged rats.

Introduction: Cognitive deficits during aging are pervasive across species and learning paradigms. One of the major mechanisms thought to play a role in age-related memory decline is dysregulated calcium (Ca ) homeostasis. Aging is associated with impaired function of several calcium-regulatory mechanisms, including calcium-binding proteins that normally support intracellular Ca regulation.

Modulation of intrinsic excitability as a function of learning within the fear conditioning circuit.

Experience-dependent neuronal plasticity is a fundamental substrate of learning and memory. Intrinsic excitability is a form of neuronal plasticity that can be altered by learning and indicates the pattern of neuronal responding to external stimuli (e.g.

Trace Fear Conditioning Differentially Modulates Intrinsic Excitability of Medial Prefrontal Cortex-Basolateral Complex of Amygdala Projection Neurons in Infralimbic and Prelimbic Cortices.

Neuronal activity in medial prefrontal cortex (mPFC) is critical for the formation of trace fear memory, yet the cellular mechanisms underlying these memories remain unclear. One possibility involves the modulation of intrinsic excitability within mPFC neurons that project to the basolateral complex of amygdala (BLA). The current study used a combination of retrograde labeling and in vitro whole-cell patch-clamp recordings to examine the effect of trace fear conditioning on the intrinsic excitability of layer 5 mPFC-BLA projection neurons in adult rats.

Learning enhances intrinsic excitability in a subset of lateral amygdala neurons.

Learning-induced modulation of neuronal intrinsic excitability is a metaplasticity mechanism that can impact the acquisition of new memories. Although the amygdala is important for emotional learning and other behaviors, including fear and anxiety, whether learning alters intrinsic excitability within the amygdala has received very little attention. Fear conditioning was combined with intracellular recordings to investigate the effects of learning on the intrinsic excitability of lateral amygdala (LA) neurons.

Learning to learn - intrinsic plasticity as a metaplasticity mechanism for memory formation.

"Use it or lose it" is a popular adage often associated with use-dependent enhancement of cognitive abilities. Much research has focused on understanding exactly how the brain changes as a function of experience. Such experience-dependent plasticity involves both structural and functional alterations that contribute to adaptive behaviors, such as learning and memory, as well as maladaptive behaviors, including anxiety disorders, phobias, and posttraumatic stress disorder.