Activation of LH GABAergic inputs counteracts fasting-induced changes in tVTA/RMTG neurons.

Dopamine neurons in the ventral tegmental area (VTA) are strongly innervated by GABAergic neurons in the 'tail of the VTA' (tVTA), also known as the rostralmedial tegmental nucleus (RMTg). Disinhibition of dopamine neurons through firing of the GABAergic neurons projecting from the lateral hypothalamus (LH) leads to reward seeking and consumption through dopamine release in the nucleus accumbens. VTA dopamine neurons respond to changes in motivational state, yet less is known about whether tVTA/RMTg GABAergic neurons or the LH GABAergic neurons that project to them are also affected by changes in motivational state, such as fasting. An acute 16 h overnight fast decreased the excitability of tVTA/RMTg GABAergic neurons of male and female mice. In addition, fasting decreased synaptic strength at LH GABA to tVTA/RMTg GABAergic synapses, indicated by reduced amplitude of optically evoked currents, decreased readily releasable pool (RRP) size and replenishment. Optical stimulation of LH GABA terminals suppressed evoked action potentials of tVTA/RMTg GABAergic neurons in unfasted mice, but this effect decreased following fasting. Furthermore, during fasting, LH GABA inputs to tVTA/RMTg neurons maintained functional connectivity during depolarization, as depolarization block was reduced following fasting. Taken together, inhibitory synaptic transmission from LH GABA inputs onto tVTA/RMTg GABAergic neurons decreases following fasting; however, ability to functionally inhibit tVTA/RMTg GABAergic neurons is preserved, allowing for possible disinhibition of dopamine neurons and subsequent foraging. KEY POINTS: While dopamine neuronal activity changes with motivational state, it is unknown if fasting influences tVTA/RMTg GABAergic neurons, a major inhibitory input to ventral tegmental area (VTA) dopamine neurons. In unfasted mice, there were sex differences in inhibitory synaptic transmission onto tVTA/RMTg GABAergic neurons. Activation of lateral hypothalamus (LH) GABAergic neurons decreases firing of tVTA/RMTg GABAergic neurons through a monosynaptic input. An acute fast decreases the excitability of tVTA/RMTg GABAergic neurons. An acute fast decreases inhibitory synaptic transmission of the LH GABA input to tVTA/RMTg GABAergic neurons in both male and female mice.

Sex differences in the effect of acute fasting on excitatory and inhibitory synapses onto ventral tegmental area dopamine neurons.

KEY POINTS: Fasting can increase motivation for food and can energize reward-seeking. Ventral tegmental area (VTA) dopamine neurons respond to motivationally relevant information and fasting can influence mesolimbic dopamine concentration. An acute overnight fast differentially alters food approach behaviours and excitatory synaptic transmission onto VTA dopamine neurons of male or female mice. While inhibitory synapses onto VTA dopamine neurons are not altered by fasting in male or female mice, male mice had strengthened excitatory synapses whereas female mice had increased endocannabinoid-mediated short-term plasticity at excitatory synapses. These results help us understand how fasting differentially influences excitatory synaptic transmission onto dopamine neurons and may inform different strategies for fasting-induced food seeking by male and female mice. ABSTRACT: Dopamine neurons in the ventral tegmental area (VTA) are important for energizing goal-directed behaviour towards food and are sensitive to changes in metabolic states. Fasting increases the incentive motivation for food and the mobilization of energy stores and has sex-dependent effects. However, it is unknown how acute fasting alters excitatory or inhibitory synaptic transmission onto VTA dopamine neurons. An acute 16 h overnight fast induced increased food-seeking behaviour that was more predominant in male mice. Fasting increased miniature excitatory postsynaptic current frequency and amplitude in male, but not female, mice. This effect was not due to altered release probability as there was no change in the paired pulse ratio, nor was it due to an altered postsynaptic response as there was no change in the AMPA receptor/NMDA receptor ratio or response to glutamate uncaging. However, this effect was consistent with an increase in the number of release sites. In addition, depolarization-induced suppression of excitation, a measure of short-term endocannabinoid-mediated plasticity, was enhanced in female but not male fasted mice. There were no fasting-induced changes at inhibitory synapses onto dopamine neurons of male or female mice. Taken together, these results demonstrate that fasting influences excitatory synapses differentially in male and female mice, but preserves inhibitory synapses onto dopamine neurons, indicating that the mesolimbic circuits of male and female mice respond differently to acute energy deprivation.

Development of an Open Face Home Cage Running Wheel for Testing Activity-Based Anorexia and Other Applications.

Running wheels for mice residing in the home cage are useful for the continuous measurement of locomotor activity for studies testing exercise interventions or exercise-induced effects on brain and metabolism. Here, we have developed an open source, printable, open-faced running wheel that is automated to collect locomotor information such as distance traveled, wheel direction, and velocity that can be binned into epochs over 24 h or multiple days. This system allows for remote data collection to avoid human interference in mouse behavioral experiments. We tested this system in an activity-based anorexia procedure. Using these wheels, we replicate previous findings that food restriction augments wheel-running activity.

Evidence for rapid gut clearance of microplastic polyester fibers fed to Chinook salmon: A tank study.

Marine and freshwater plastic pollution is a challenging issue receiving large amounts of research and media attention. Yet, few studies have documented the impact of microplastic ingestion to aquatic organisms. In the Pacific Northwest, Chinook salmon are a culturally and commercially significant fish species. The presence of marine and freshwater microplastic pollution is well documented in Chinook salmon habitat, yet no research has investigated the impacts to salmon from microplastic ingestion. The majority of the marine microplastics found in the Salish Sea are microfibers, synthetic extruded polymers that come from commonly worn clothing. To understand the potential impacts of microfiber ingestion to fish, we ran a feeding experiment with juvenile Chinook salmon to determine if ingested fibers are retained or digestion rates altered over a 10 day digestion period. The experiment was completed in two trials, each consisted of 20 control and 20 treatment fish. Treatment fish were each fed an amended ration of 12 food pellets spiked with 20 polyester microfibers and control fish were fed the same ration without added microfibers. Fish were sampled at day 0, 3, 5, 7, and 10 to assess if fibers were retained in their gastrointestinal tract and to determine the rate of digestion. Fibers for the experiment came from washing a red polyester fleece jacket in a microfiber retention bag. Fibers had a mean length of 4.98 mm. Results showed fish were able to clear up to 94% of fed fibers over 10 days. Differences in mean gastrointestinal mass were not statistically significant at any sampled time between treatment and controls, suggesting that the ingestion of microfibers did not alter digestion rates. Further work is needed to understand if repeated exposures, expected in the environment, alter digestion or food assimilation for growth.

Dopamine Inputs from the Ventral Tegmental Area into the Medial Prefrontal Cortex Modulate Neuropathic Pain-Associated Behaviors in Mice.

The medial prefrontal cortex (mPFC) is a brain region involved in the affective components of pain and undergoes plasticity during the development of chronic pain. Dopamine (DA) is a key neuromodulator in the mesocortical circuit and modulates working memory and aversion. Although DA inputs into the mPFC are known to modulate plasticity, whether and how these inputs affect pain remains incompletely understood. By using optogenetics, we find that phasic activation of DA inputs from the ventral tegmental area (VTA) into the mPFC reduce mechanical hypersensitivity during neuropathic pain states. Mice with neuropathic pain exhibit a preference for contexts paired with photostimulation of DA terminals in the mPFC. Fiber photometry-based calcium imaging reveals that DA increases the activity of mPFC neurons projecting to the ventrolateral periaqueductal gray (vlPAG). Together, our findings indicate an important role of mPFC DA signaling in pain modulation.

Diversity in the lateral hypothalamic input to the ventral tegmental area.

The obesity epidemic is one of the biggest health challenges globally and rates have tripled since 1975. Overeating is the largest determinant of obesity, yet little is understood of the neural mechanisms underlying why individuals consume food regardless of satiety. The lateral hypothalamic (LH) input to the ventral tegmental area (VTA) has been critically implicated in regulating appetitive and reward-related behaviours. However, these projections are genetically heterogeneous and have different responses to leptin. Therefore each of these projections may play a different role in modulating the VTA. This review characterizes each of these known LH to VTA projections in their roles in regulating appetitive behaviour. This article is part of the Special Issue entitled 'Hypothalamic Control of Homeostasis'.

Effects of bed height on the biomechanics of hospital bed entry and egress.

BACKGROUND: Although a significant proportion of patient falls in hospitals occur in the vicinity of the hospital bed, little is known about the contribution of bed height to fall risk. OBJECTIVE: To compare lower extremity joint torques and angles during hospital bed entry and egress at two bed heights. METHODS: Twelve adults (age > 55) were purposively selected and had variety of strength and mobility limitations. Biomechanical data for this pilot study were collected with three digital video cameras and processed to obtain estimates for joint torques and included angles. RESULTS: At the low bed height, hip torque for bed entry was significantly higher, and hip, knee, and ankle flexion angles were significantly smaller. The absence of significant differences in knee and ankle torques were the result of a compensation strategy that shifts the center of mass forward by flexing the torso during low bed ingress. Torque data from the egress motion were similar, however 50% of participants were unable to rise from the low bed without assistance. CONCLUSIONS: Healthcare providers should be aware that low bed heights pose safety risks to the population for which they were designed-elderly persons at high risk for falling.