Neuroscience
-
Nicotinic receptors have been linked to a wide range of cognitive and behavioral functions, but surprisingly little is known about their involvement in cost benefit decision making. The goal of these experiments was to determine how nicotinic acetylcholine receptor (nAChR) expression is related to two forms of cost benefit decision making. Male Long Evans rats were tested in probability- and delay-discounting tasks, which required discrete trial choices between a small reward and a large reward associated with varying probabilities of omission and varying delays to reward delivery, respectively. ⋯ Additionally, trends were found suggesting that choice of the large costly reward in both discounting tasks was inversely related to α4β2 receptor binding in the medial prefrontal cortex and nucleus accumbens shell. Similar trends suggested that choice of the large delayed reward in the delay discounting task was inversely related to α4β2 receptor binding in the orbitofrontal cortex, nucleus accumbens core, and basolateral amygdala, as well as to α7 receptor binding in the basolateral amygdala. These data suggest that nAChRs (particularly α4β2) play both unique and common roles in decisions that require consideration of different types of reward costs.
-
Here we investigate the contribution of striatal dopamine receptors (D1) to the influence of reward-magnitude on learning. Pigeons (Columba livia) were trained on a discrimination-task with two pairs of stimuli; correct discrimination resulted in a large reward in one pair of stimuli and in a small reward in the other pair. Acquisition of the discrimination-task was accompanied by intracranial injections to the medial striatum, either of a dopamine-antagonist (Sch23390) or of vehicle. ⋯ Consequently, it appears that not learning per se but the effect of reward-magnitude on learning is mediated through D1 receptors in the striatum. We argue that the injections of dopamine-antagonist cause a shift in strategy underlying learning. In the control-condition animals rely on positive feedback and thus learning is affected by the magnitude of the contingent reward; in the antagonist-condition, however, learning might rely on negative feedback and is thus insensitive to reward-magnitude.
-
Cerebral ischemia, traumatic brain injury, intracerebral hemorrhage and other brain insults trigger neurogenesis in the subventricular zone and hippocampal subgranular zone, and newly formed blood vessels promote the migration of these new neuronal cells to damaged brain regions. The molecular steps involved in brain injury-induced angiogenesis and neurogenesis are unclear. ⋯ Intracerebroventricular injection of MMP-9 siRNA reduced these ICH-induced increases. These findings suggest that MMP-9 may promote angiogenesis and neurogenesis during recovery from ICH.
-
In adult rats, trans-resveratrol attenuates kainic acid (KA)-induced convulsions and the associated hippocampal neurotoxicity. Increased neuronal survival was correlated with reduced lipid peroxidation. Since free radical generation after KA is age dependent and does not correlate with the onset of seizure-induced injury, the present study investigated whether daily trans-resveratrol treatment in development could protect the juvenile hippocampus from seizures and onset of damage at postnatal (P) day 21. ⋯ Glutamate (100 μM) to stimulate peroxidation products was significant at young ages but was much greater at older ages. After KA, elevated MDA levels were observed at 24h but only in adult preparations. Thus, while antioxidant therapy with trans-resveratrol may be considered as an adjunctive therapy to hinder epileptic activity and neurodegeneration at adult ages, it had only modest effects at young ages when production of free radicals within limbic structures is limited in this experimental model of seizures.
-
Oxidative stress and inflammation play an integral role in the pathogenesis of cerebral ischemia that leads to a cascade of events culminating in the death of neurons and their supporting structures. The signaling pathways that link these events are not fully understood. Recent studies have demonstrated a close link between the nuclear factor-κB (NF-κB) signaling pathway and cerebral ischemia/reperfusion (I/R)-induced inflammation. ⋯ Moreover, immunohistochemical and Western blot analyses clearly demonstrated that naringenin treatment limits glial activation and downregulates the NF-κB expression level and their target genes. These results show, prophylactic treatment with naringenin improved functional outcomes and abrogated the ischemic brain injury by suppressing NF-κB-mediated neuroinflammation. The present study suggests that naringenin may be used as a potential neuroprotectant in patients at high risk of ischemic stroke.