Selective targeting of Scn8a prevents seizure development in a mouse model of mesial temporal lobe epilepsy.

We previously found that genetic mutants with reduced expression or activity of Scn8a are resistant to induced seizures and that co-segregation of a mutant Scn8a allele can increase survival and seizure resistance of Scn1a mutant mice. In contrast, Scn8a expression is increased in the hippocampus following status epilepticus and amygdala kindling. These findings point to Scn8a as a promising therapeutic target for epilepsy and raise the possibility that aberrant overexpression of Scn8a in limbic structures may contribute to some epilepsies, including temporal lobe epilepsy.

Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss - A Common Hereditary Deafness.

Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood.

Differential effects of massed and spaced training on place and response learning: A memory systems perspective.

Studies employing brain lesion or intracerebral drug infusions in rats have demonstrated a double dissociation between the roles of the hippocampus and dorsolateral striatum in place and response learning. The hippocampus mediates a rapid cognitive learning process underlying place learning, whereas the dorsolateral striatum mediates a relatively slower learning process in which stimulus-response habits underlying response learning are acquired in an incremental fashion. One potential implication of these findings is that hippocampus-dependent learning may benefit from a relative massing of training trials, whereas dorsal striatum-dependent learning may benefit from a relative distribution of training trials.

Knockdown of tropomyosin-related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress-induced cross-sensitization to amphetamine in rats.

The nucleus accumbens (NAc) is a critical brain region for the rewarding effects of drugs of abuse. Brain-derived neurotrophic factor (BDNF) can facilitate stress- and drug-induced neuroadaptation in the mesocorticolimbic system. BDNF-containing projections to the NAc originate from the ventral tegmental area (VTA) and the prefrontal cortex, and BDNF release activates tropomyosin-related kinase B (TrkB).

The amygdala and emotional modulation of competition between cognitive and habit memory.

The basolateral amygdala (BLA) is implicated in the neurobiology of emotion, and can also modulate the cognitive and habit memory processes mediated by the hippocampus and dorsal striatum, respectively. In a dual-solution task that can be acquired using either hippocampus-dependent or dorsal striatal-dependent learning, peripheral or intra-BLA infusion of the anxiogenic alpha(2)-adrenoreceptor antagonist RS 79948 biases rats towards the use of habit learning. In view of evidence that anxiety can promote relapse into habitual and maladaptive human behaviors, understanding the mechanism(s) by which emotional arousal can influence the relative use of multiple memory systems may prove clinically relevant.

Habit learning in Tourette syndrome: a translational neuroscience approach to a developmental psychopathology.

Background: The etiology of Tourette syndrome (TS) involves disturbances in the structure and function of the basal ganglia. The basal ganglia mediate habit learning.

Objective: To study habit learning in persons with TS.

Amygdala and "emotional" modulation of the relative use of multiple memory systems.

The basolateral amygdala modulates the cognitive and habit memory processes mediated by the hippocampus and caudate nucleus, respectively. The present experiments used a plus-maze task that can be acquired using either hippocampus-dependent "place" learning or caudate-dependent "response" learning to examine whether peripheral or intra-basolateral amygdala injection of anxiogenic drugs would bias rats towards the use of a particular memory system. In Experiment 1, adult male Long-Evans rats were trained to swim from the same start point to an escape platform located in a consistent goal arm, and received pre-training peripheral injections of the alpha(2)-adrenoceptor antagonists yohimbine (2.

Post-training reversible inactivation of hippocampus reveals interference between memory systems.

A post-training reversible lesion technique was used to examine the effects of neural inactivation of the dorsal hippocampus on place and response learning. Male Long-Evans rats trained in one of two versions of a water plus-maze task received post-training intra-hippocampal infusions of the local anesthetic drug bupivacaine (0.75% solution, 0.