Experience alters hippocampal and cortical network communication via a KIBRA-dependent mechanism.

Synaptic plasticity is hypothesized to underlie "replay" of salient experience during hippocampal sharp-wave/ripple (SWR)-based ensemble activity and to facilitate systems-level memory consolidation coordinated by SWRs and cortical sleep spindles. It remains unclear how molecular changes at synapses contribute to experience-induced modification of network function. The synaptic protein KIBRA regulates plasticity and memory.

A Lightweight Drive Implant for Chronic Tetrode Recordings in Juvenile Mice.

In vivo electrophysiology provides unparalleled insight into the sub-second-level circuit dynamics of the intact brain and represents a method of particular importance for studying mouse models of human neuropsychiatric disorders. However, such methods often require large cranial implants, which cannot be used in mice at early developmental time points. As such, virtually no studies of in vivo physiology have been performed in freely behaving infant or juvenile mice, despite the fact that a better understanding of neurological development in this critical window would likely provide unique insights into age-dependent developmental disorders such as autism or schizophrenia.

A novel, lightweight drive implant for chronic tetrode recordings in juvenile mice.

Short Abstract: We describe a novel micro-drive design, surgical implantation procedure, and post-surgery recovery strategy that allows for chronic field and single-unit recordings from up to sixteen brain regions simultaneously in juvenile and adolescent mice across a critical developmental window from p20 to p60 and beyond.

Long Abstract: electrophysiology provides unparalleled insight into sub-second-level circuit dynamics of the intact brain and represents a method of particular importance for studying mouse models of human neuro-psychiatric disorders. However, such methods often require large cranial implants which cannot be used in mice at early developmental timepoints.

KIBRA regulates activity-induced AMPA receptor expression and synaptic plasticity in an age-dependent manner.

A growing body of human literature implicates KIBRA in memory and neurodevelopmental disorders. Memory and the cellular substrates supporting adaptive cognition change across development. Using an inducible KIBRA knockout mouse, we demonstrate that adult-onset deletion of KIBRA in forebrain neurons impairs long-term spatial memory and long-term potentiation (LTP).

Repetitive stress in mice causes migraine-like behaviors and calcitonin gene-related peptide-dependent hyperalgesic priming to a migraine trigger.

Migraine is one of the most disabling disorders worldwide but the underlying mechanisms are poorly understood. Stress is consistently reported as a common trigger of migraine attacks. Here, we show that repeated stress in mice causes migraine-like behaviors that are responsive to a migraine therapeutic.

Non-invasive dural stimulation in mice: A novel preclinical model of migraine.

Background: Migraine is characterized by a collection of neurological symptoms in the absence of injury or damage. However, several common preclinical migraine models require significant damage to the skull to stimulate the dura mater, the likely source of afferent signaling leading to head pain. The goal of this study was to determine whether dural stimulation can be performed in mice using an injection that does not cause injury or damage.

Comparative transcriptome profiling of the human and mouse dorsal root ganglia: an RNA-seq-based resource for pain and sensory neuroscience research.

Molecular neurobiological insight into human nervous tissues is needed to generate next-generation therapeutics for neurological disorders such as chronic pain. We obtained human dorsal root ganglia (hDRG) samples from organ donors and performed RNA-sequencing (RNA-seq) to study the hDRG transcriptional landscape, systematically comparing it with publicly available data from a variety of human and orthologous mouse tissues, including mouse DRG (mDRG). We characterized the hDRG transcriptional profile in terms of tissue-restricted gene coexpression patterns and putative transcriptional regulators, and formulated an information-theoretic framework to quantify DRG enrichment.

Dural stimulation in rats causes brain-derived neurotrophic factor-dependent priming to subthreshold stimuli including a migraine trigger.

Migraine is one of the most common and most disabling disorders. Between attacks, migraine patients are otherwise normal but are sensitized to nonnoxious events known as triggers. The purpose of these studies was to investigate whether a headache-like event causes sensitization, or priming, to subsequent subthreshold events.