A simple action reduces high fat diet intake and obesity in mice.

Diets that are high in fat cause over-eating and weight gain in multiple species of animals, suggesting that high dietary fat is sufficient to cause obesity. However, high-fat diets are typically provided freely to animals in obesity experiments, so it remains unclear if high-fat diets would still cause obesity if they required more effort to obtain. We hypothesized that unrestricted and easy access is necessary for high-fat diet induced over-eating, and the corollary that requiring mice to perform small amounts of work to obtain high-fat diet would reduce high-fat diet intake and associated weight gain.

Age-related deficits in neuronal physiology and cognitive function are recapitulated in young mice overexpressing the L-type calcium channel, Ca 1.3.

The calcium dysregulation hypothesis of brain aging posits that an age-related increase in neuronal calcium concentration is responsible for alterations in a variety of cellular processes that ultimately result in learning and memory deficits in aged individuals. We previously generated a novel transgenic mouse line, in which expression of the L-type voltage-gated calcium, Ca 1.3, is increased by ~50% over wild-type littermates.

Turning strains into strengths for understanding psychiatric disorders.

There is a paucity in the development of new mechanistic insights and therapeutic approaches for treating psychiatric disease. One of the major challenges is reflected in the growing consensus that risk for these diseases is not determined by a single gene, but rather is polygenic, arising from the action and interaction of multiple genes. Canonically, experimental models in mice have been designed to ascertain the relative contribution of a single gene to a disease by systematic manipulation (e.

Development of low-cost cardiac and skeletal muscle laboratory activities to teach physiology concepts and the scientific method.

Anatomy and Physiology courses taught at community colleges tend to focus laboratory hours primarily on anatomy as opposed to physiology. However, research demonstrates that, when instructors utilize active learning approaches (such as in laboratory settings) where students participate in their own learning, students have improved outcomes, such as higher test scores and better retention of material. To provide community college students with opportunities for active learning in physiology, we developed two laboratory exercises to engage students in cardiac and skeletal muscle physiology.

Environmental variables that ameliorate extinction learning deficits in the 129S1/SvlmJ mouse strain.

Fear conditioning is an associative learning process by which organisms learn to avoid environmental stimuli that are predictive of aversive outcomes. Fear extinction learning is a process by which avoidance of fear-conditioned stimuli is attenuated when the environmental stimuli is no longer predictive of the aversive outcome. Aberrant fear conditioning and extinction learning are key elements in the development of several anxiety disorders.

The ubiquitin-proteasome system functionally links neuronal Tomosyn-1 to dendritic morphology.

Altering the expression of Tomosyn-1 (Tomo-1), a soluble, R-SNARE domain-containing protein, significantly affects behavior in mice, , and Yet, the mechanisms that modulate Tomo-1 expression and its regulatory activity remain poorly defined. Here, we found that Tomo-1 expression levels influence postsynaptic spine density. Tomo-1 overexpression increased dendritic spine density, whereas Tomo-1 knockdown (KD) decreased spine density.

Dynamic Partitioning of Synaptic Vesicle Pools by the SNARE-Binding Protein Tomosyn.

Unlabelled: Neural networks engaged in high-frequency activity rely on sustained synaptic vesicle recycling and coordinated recruitment from functionally distinct synaptic vesicle (SV) pools. However, the molecular pathways matching neural activity to SV dynamics and release requirements remain unclear. Here we identify unique roles of SNARE-binding Tomosyn1 (Tomo1) proteins as activity-dependent substrates that regulate dynamics of SV pool partitioning at rat hippocampal synapses.

Pharmacological correction of obesity-induced autophagy arrest using calcium channel blockers.

Autophagy deregulation during obesity contributes to the pathogenesis of diverse metabolic disorders. However, without understanding the molecular mechanism of obesity interference in autophagy, development of therapeutic strategies for correcting such defects in obese individuals is challenging. Here we show that a chronic increase of the cytosolic calcium concentration in hepatocytes during obesity and lipotoxicity attenuates autophagic flux by preventing the fusion between autophagosomes and lysosomes.

Distinct actions of Rab3 and Rab27 GTPases on late stages of exocytosis of insulin.

Rab GTPases associated with insulin-containing secretory granules (SGs) are key in targeting, docking and assembly of molecular complexes governing pancreatic β-cell exocytosis. Four Rab3 isoforms along with Rab27A are associated with insulin granules, yet elucidation of the distinct roles of these Rab families on exocytosis remains unclear. To define specific actions of these Rab families we employ Rab3GAP and/or EPI64A GTPase-activating protein overexpression in β-cells from wild-type or Ashen mice to selectively transit the entire Rab3 family or Rab27A to a GDP-bound state.

Efficient transfection of dissociated mouse chromaffin cells using small-volume electroporation.

We have developed an improved procedure for isolating and transfecting a chromaffin cell-enriched population of primary cells from adult mouse adrenal glands. Significantly, the parameters of a novel electroporation transfection technique were optimized to achieve an average transfection efficiency of 45 % on the small number of cells derived from the mouse glands. Such transfection efficiency was previously unachievable with the electroporation protocols conventionally used with bovine chromaffin cells, even with use of large cell numbers.

Orbitofrontal cortex and basolateral amygdala lesions result in suboptimal and dissociable reward choices on cue-guided effort in rats.

The orbitofrontal cortex (OFC) and basolateral nucleus of the amygdala (BLA) are important neural regions in responding adaptively to changes in the incentive value of reward. Recent evidence suggests these structures may be differentially engaged in effort and cue-guided choice behavior. In 2 T-maze experiments, we examined the effects of bilateral lesions of either BLA or OFC on (1) effortful choices in which rats could climb a barrier for a high reward or select a low reward with no effort and (2) effortful choices when a visual cue signaled changes in reward magnitude.

Reversal-specific learning impairments after a binge regimen of methamphetamine in rats: possible involvement of striatal dopamine.

A growing body of evidence indicates that protracted use of methamphetamine (mAMPH) causes long-term impairments in cognitive function in humans. Aside from the widely reported problems with attention, mAMPH users exhibit learning and memory deficits, particularly on tasks requiring response control. Although binge mAMPH administration to animals results in cognitive deficits, few studies have attempted to test behavioral flexibility in animals after mAMPH exposure.