Neuroscience
-
The ability to process information regarding reward-predictive cues involves a diverse network of neural substrates. Given the importance of the nucleus accumbens (NAc) and the basolateral amygdala (BLA) in associative reward processes, recent research has examined the functional importance of BLA-NAc interactions. Here, multi-neuron extracellular recordings of NAc neurons coupled to microinfusion of GABAA and GABAB agonists into the BLA were employed to determine the functional contribution of the BLA to phasic neural activity across the NAc core and shell during a cued-instrumental task. ⋯ Additionally, phasic increases in firing rate in the core (not shell) immediately following the lever press response were also significantly reduced following BLA manipulation. Concurrent with these neural changes, BLA inactivation caused a significant increase in latency to respond for rewards and a decrease in the percentage of trials in which animals made a conditioned approach to the cue. Together, these results suggest that an excitatory projection from the BLA provides a selective contribution to conditioned neural excitations of NAc core neurons during a cued-instrumental task, providing insight into the underlying neural circuitry that mediates responding to reward-predictive cues.
-
The protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6K) signaling pathway, as a central controller of cell growth, proliferation, survival, and differentiation in response to extracellular signals, growth factors, nutrient availability, energy status of the cell, and stress, has recently gained attention in neuroscience. The effects of this signaling pathway on repair of spinal cord injury (SCI), however, have not been well elucidated. ATP is increasingly recognized as an important regulator of signal transduction pathways, and plays important roles in functional recovery after nervous system injury. ⋯ We observed the effectiveness of the activated Akt/mTOR/p70S6K signaling pathway in improving locomotor recovery, significantly increasing the expression of nestin, neuronal nuclei (NeuN), neuron specific enolase (NSE), and neurofilament 200 (NF200), and relatively inhibiting excessive reactive astrogliosis after SCI in a rapamycin-sensitive manner. We concluded that ATP injection produced a significant activation of the Akt/mTOR/p70S6K signaling pathway in the injured spinal cord and that enhancement of rapamycin-sensitive signaling produces beneficial effects on SCI-induced motor function defects and repair potential. We suggest that modulation of this protein kinase signaling pathway activity should be considered as a potential therapeutic strategy for SCI.
-
Although respiratory complications significantly contribute to morbidity/mortality in advanced myelin disorders, little is known concerning mechanisms whereby dysmyelination impairs ventilation, or how patients compensate (i.e. plasticity). To establish a model for studies concerning mechanisms of ventilatory impairment/compensation, we tested the hypotheses that respiratory function progressively declines in a model of CNS dysmyelination, the Long Evans shaker rat (les). The observed impairment is associated with abnormal inspiratory neural output. ⋯ In WT rats, phrenic activity was progressive and augmenting; in les rats, phrenic activity was decrementing with asynchronized, multipeaked activity. Thus, although ventilatory capacity is maintained in young, dysmyelinated rats, ventilatory impairment develops with age, possibly through discoordination in respiratory motor output. This study is the first reporting age-related breathing abnormalities in a rodent dysmyelination model, and provides the foundation for mechanistic studies of respiratory insufficiency and therapeutic interventions.
-
There is growing evidence that lesions of the anterior thalamic nuclei cause long-lasting intrinsic changes to retrosplenial cortex, with the potential to alter its functional properties. The present study had two goals. The first was to identify the pattern of changes in eight markers, as measured by in-situ hydridisation, in the granular retrosplenial cortex (area Rgb) following anterior thalamic lesions. ⋯ In Experiment 2, wheat germ agglutin (WGA) was injected into the anterior thalamic nuclei in rats given different survival times, sometimes in combination with the retrograde, fluorescent tracer, Fast Blue. Dense aggregations of retrogradely labeled cells were always found in lamina VI of granular retrosplenial cortex, but additional labeled cells in lamina II were only found: (1) in WGA cases, that is never after Fast Blue injections, and (2) after longer WGA survival times (3 days). These layer II Rgb cells are likely to have been trans-neuronally labeled, revealing a pathway from lamina II of Rgb to those deeper retrosplenial cells that project directly to the anterior thalamic nuclei.
-
Alzheimer's disease (AD) is a neurodegenerative disease. There are a limited number of therapeutic options available for the treatment of AD. Curcuminoids (a mixture of bisdemethoxycurcumin, demethoxycurcumin and curcumin) is the main chemical constituent found in turmeric, a well known curry spice, having potential in the treatment of AD. ⋯ Of these, demethoxycurcumin was the most effective showing a 350.1% increase (P<0.01) at 30 mg/kg compared to the neurotoxin group. When studied for their effect on camkIV expression after longer treatment in the hippocampus, only demethoxycurcumin at 30 mg/kg increased levels to 421.2%. These compounds salvaged PSD-95, synaptophysin and camkIV expression levels in the hippocampus in the rat AD model, which suggests multiple target sites with the potential of curcuminoids in spatial memory enhancing and disease modifying in AD.