Neural Activity In Rats Research Articles

Dorsolateral Striatal proBDNF Improves Reversal Learning by Enhancing Coordination of Neural Activity in Rats.

Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. The dorsolateral striatum (DLS) is part of corticostriatal circuits that is involved in flexible behavior. Pro-brain-derived neurotrophic factor (proBDNF) can enhance fear memory extinction and weaken synaptic transmission, which may enable flexible adaptations. However, the role of proBDNF in cognitive flexibility is unclear. Here, through infusion of cleavage-resistant proBDNF or its antibody into the DLS of rats, we sought evidence for the influences by employing behavioral tests, immunoblotting, immunocytochemistry, and electrophysiological recoding. Infusion of proBDNF significantly facilitated reversal learning while inhibiting DLS proBDNF by anti-proBDNF antibody impaired the behavioral performance. Furthermore, elevation of DLS proBDNF facilitated neural correlate with reversal performance while blocking proBDNF expression decayed the spike-field coupling during the correct turning. Reversal learning induced increases in endogenous neuronal proBDNF, with a strong correlation between DLS and infralimbic cortex (IL), but not prelimbic cortex (PL) or sensory-motor cortex (SM). Importantly, blockade of IL proBDNF disrupted the DLS-mediated reversal learning enhancement, implying the involvement of both IL and DLS regions in reversal habitual behavior. Taken together, our findings provide first evidence for the essential role of the DLS proBDNF in cognitive flexibility and suggest that proBDNF-mediated neural function could be the mechanism.

Distinct recruitment of dorsomedial and dorsolateral striatum erodes with extended training.

Hypotheses of striatal orchestration of behavior ascribe distinct functions to striatal subregions, with the dorsolateral striatum (DLS) especially implicated in habitual and skilled performance. Thus neural activity patterns recorded from the DLS, but not the dorsomedial striatum (DMS), should be correlated with habitual and automatized performance. Here, we recorded DMS and DLS neural activity in rats during training in a task promoting habitual lever pressing. Despite improving performance across sessions, clear changes in corresponding neural activity patterns were not evident in DMS or DLS during early training. Although DMS and DLS activity patterns were distinct during early training, their activity was similar following extended training. Finally, performance after extended training was not associated with DMS disengagement, as would be predicted from prior work. These results suggest that behavioral sequences may continue to engage both striatal regions long after initial acquisition, when skilled performance is consolidated.

Pre-administration of low-dose methamphetamine enhances movement and neural activity after high-dose methamphetamine administration in the striatum

Methamphetamine (METH) is a powerful stimulant drug of abuse, with potent addictive and neurotoxic properties. In this study, the effects of low-dose METH administration prior to high-dose METH administration on movement and neural activity in rats were examined. Rats were administered low-dose (1 mg/kg/day) METH or saline for 5 consecutive days (m5 and s5, respectively), followed by high-dose (10 mg/kg) METH on day 6 (m5M and s5M, respectively). An accelerometer was used to evaluate the frequency of movement when rats were placed in a cage for 30 min. The expression of c-fos, a neuronal activity marker, in the striatum was analyzed using immunohistochemistry. Striatal protein expression of neuronal markers, including vesicular glutamate transporter 2 (VGLUT2), glutamate decarboxylase 67 (GAD67), tyrosine hydroxylase (TH), tryptophan hydroxylase 2 (TPH2), and the glial marker, glial fibrillary acidic protein (GFAP), was analyzed by western blot. Accelerometer counts and the numbers of c-fos-positive cells in the striatum were significantly higher in the m5M than in the s5, m5, and s5M groups. The expression levels of VGLUT2 and GAD67, but not those of TH, TPH2, or GFAP, were significantly higher in the m5M than in the s5M group. These results suggest that pre-administration of low-dose METH prior to high-dose METH administration in rats may alter excitatory and inhibitory neurons in the striatum, thereby affecting movement and neural activity in rats.

Hippocampal proBDNF facilitates place learning strategy associated with neural activity in rats

Mature brain-derived neurotrophic factor has been shown to have a promotive effect on synaptic plasticity and spatial memory. The precursor of BDNF (proBDNF) has emerged as a protein against its mature form. However, it is unknown whether and how proBDNF regulates neural excitability and spatial behavior. Through infusion of cleavage-resistant proBDNF or its antibody into HPC, we sought evidence for the influences by employing multiple behavioral tests and recording hippocampal single-unit activity. Our behavioral findings showed that proBDNF induced beneficial effects on spatial learning by facilitating the use of the place strategy and inhibiting the response strategy, including (1) using more place search strategies but less response strategies, and (2) increasing the number of rats in choosing place strategies but not response strategies. Intriguingly, infusion of an anti-proBDNF antibody did not affect rats' training process but rendered the adaption to learning reversal training more difficult, indicating deficits in choosing the proper learning strategy. The training-induced increase in proBDNF promoted the firing rate of pyramidal neurons but not fast-spiking (FS) interneurons. Importantly, endogenous proBDNF facilitated the neural correlate of spatial, but not response, learning behavior. However, the anti-proBDNF antibody effectively reversed the strategy preference and inhibited neural activity. We herein propose that proBDNF exerts pivotal effects on neural excitability and the use of cognitive strategies to facilitate the spatial learning process.

Regulation of hypoxia-inducible factor-α isoforms and redox state by carotid body neural activity in rats.

Previous studies reported that chronic intermittent hypoxia (CIH) results in an imbalanced expression of hypoxia-inducible factor-α (HIF-α) isoforms and oxidative stress in rodents, which may be due either to the direct effect of CIH or indirectly via hitherto uncharacterized mechanism(s). As neural activity is a potent regulator of gene transcription, we hypothesized that carotid body (CB) neural activity contributes to CIH-induced HIF-α isoform expression and oxidative stress in the chemoreflex pathway. Experiments were performed on adult rats exposed to CIH for 10 days. Rats exposed to CIH exhibited: increased HIF-1α and decreased HIF-2α expression; increased NADPH oxidase 2 and decreased superoxide dismutase 2 expression; and oxidative stress in the nucleus tractus solitarius and rostral ventrolateral medulla as well as in the adrenal medulla (AM), a major end organ of the sympathetic nervous system. Selective ablation of the CB abolished these effects. In the AM, sympathetic activation by the CB chemoreflex mediates CIH-induced HIF-α isoform imbalance via muscarinic acetylcholine receptor-mediated Ca(2+) influx, and the resultant activation of mammalian target of rapamycin pathway and calpain proteases. Rats exposed to CIH presented with hypertension, elevated sympathetic activity and increased circulating catecholamines. Selective ablation of either the CB (afferent pathway) or sympathetic innervation to the AM (efferent pathway) abolished these effects. These observations uncover CB neural activity-dependent regulation of HIF-α isoforms and the redox state by CIH in the central and peripheral nervous systems associated with the chemoreflex.

Protective Effect of Soybean-Derived Phosphatidylserine on the Trimethyltin-Induced Learning and Memory Deficits in Rats

The present study examined the effects of soybean-derived phosphatidylserine (SB-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The cognitive improving efficacy of SB-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing cholineacetyl transferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. A positron emission tomography (PET) scanning the rat brain was by performed administer 18F-Fluorodeoxy-glucose (18F-FDG). The rats with TMT injection showed impaired learning and memory of the tasks and treatment with SB-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the 2nd day compared to that of the MCT group. In the retention test, the SB-PS group showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, SB-PS 50 group significantly alleviated the loss of acetyl cholinergic neurons in the hippocampus compared to that of the MCT group. Treatment with SB-PS significantly increased the CREB positive neurons in the hippocampus as compared to that of the MCT group. In addition, SB-PS groups increased the glucose uptake in the hippocampus and SB-PS 50 group increased the glucose uptake in the frontal lobe, as compared to that of the MCT group. These results suggest that SB-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.

English

Arsenite (Arsenic III) is ubiquitous and a widely distributed environmental toxin implicated in the aetiology of several neurological disorders. It is found in sea food, chemicals and pesticides. As(III) is also a mitochondria poison that induces reactive oxygen species (ROS) formation and membrane distortion. This study is aimed at proposing an in vitro method to detecting neural activity in rat’s brain treated with As(III). Neurotoxic effects of As(III) on brain slices in rat model and description of its varying cytotoxic pathways using electrophysiological approach shall constitute another focus of the study. Brain slices were sub-cultured in Artificial Cerebro Spinal Fluid (ACSF) and treated with 50 µl of 0.1 M arsenite for 30 min. A superficial pin electrode was used to record the electrical activity following each stimulation. The spike train was analyzed to obtain the frequencies in db and this was recorded for 0.00 to 0.16 ms. As(III) induced changes in the electrical activities of the brain to a varying extent and such changes vary with the cytotoxic pathways for such regions. In the parietal cortex and upper brainstem, As(III) reduced the firing rate when compared with increased neuronal firing rates in the lower brainstem as depicted by spike peaks. Key words: Arsenic, neuron, peaks, frequency, toxicity, action potential.

Electroplated Nickel Multielectrode Microprobes With Flexible Parylene Cable for Neural Recording and Stimulation

We design, fabricate, and characterize nickel-based multielectrode microprobes integrated with flexible parylene cable employing low-cost nickel electroplating process, intended for multichannel recording and stimulation of neurons in the brain. Electroplated nickel microprobes, which are encapsulated with parylene for biocompatibility, are more mechanically robust than brittle silicon-based ones. The selectively integrated flexible parylene cable facilitates the connection with external circuits and reduces the packaging requirements. The mechanical and electrical characterizations have been performed. Using the microprobes, the spontaneous neural activity in rat's hippocampus is recorded and the wing beat of tethered worker honeybees is initiated by delivering the stimulating pulse into the optic lobes.

Mild Traumatic Brain Injury Is Associated with Impaired Hippocampal Spatiotemporal Representation in the Absence of Histological Changes

Mild traumatic brain injury (mTBI) accounts for the majority of head trauma cases. Despite some lasting cognitive, emotional, and behavioral deficits, there are frequently no overt morphological defects, suggesting that changes may result from alterations in the physiology of individual neurons. We investigated hippocampal neural activity in rats during a working memory task to determine the effect of mTBI on cellular physiology. Male Sprague-Dawley rats (300-350 g) underwent mTBI via lateral fluid percussion (1.5 atm), and were compared with sham-operated rats. The rats then underwent bilateral implantation of electrodes into the CA1 and CA3 hippocampal subfields and were trained to perform in a delayed nonmatch-to-place swim T-maze. Single-neuron activity was analyzed during task performance 30-90 days after trauma. There were no histological differences between control and mTBI rats. Stereological analysis demonstrated no neuronal loss. Nevertheless, rats subjected to mTBI demonstrated significantly poorer performance on the task with increasing delay. Examination of single-neuron spiking activity revealed no significant difference in firing rates or spike characteristics, but rats exposed to mTBI were found to have significantly fewer cells with activity spatiotemporally correlated with location in the maze ("task-specific cells," p<0.05 by Fisher's exact test). Memory deficits, including disorganized patterns of hippocampal neural activity after mTBI, were seen in rats. Because it is seen in the absence of clear morphological defects, these data suggest that functional impairment after mTBI may result from alterations in the activity of individual neurons.

Krill-Derived Phosphatidylserine Improves TMT-Induced Memory Impairment in the Rat

The present study examined the effects of krill-derived phosphatidylserine (Krill-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered vehicle (medium-chain triglyceride: MCT) or Krill-PS (50, 100 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of Krill-PS in TMT-induced amnesic rats was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. The rats with TMT injection showed impaired learning and memory of the tasks and treatment with Krill-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the 2nd and 4th day compared to that of the MCT group (p<0.05). In the retention test, the Krill-PS+MCT groups showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, Krill-PS 50+MCT group significantly alleviated the loss of acetylcholinergic neurons in the hippocampus and medial septum compared to that of the MCT group. Treatment with Krill-PS significantly increased the CREB positive neurons in the hippocampal CA1 area as compared to that of the MCT group. These results suggest that Krill-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.

Chronic Treatment with Squid Phosphatidylserine Activates Glucose Uptake and Ameliorates TMT-Induced Cognitive Deficit in Rats via Activation of Cholinergic Systems

The present study examined the effects of squid phosphatidylserine (Squid-PS) on the learning and memory function and the neural activity in rats with TMT-induced memory deficits. The rats were administered saline or squid derived Squid-PS (Squid-PS 50 mg kg−1, p.o.) daily for 21 days. The cognitive improving efficacy of Squid-PS on the amnesic rats, which was induced by TMT, was investigated by assessing the passive avoidance task and by performing choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) immunohistochemistry. 18F-Fluorodeoxyglucose and performed a positron emission tomography (PET) scan was also performed. In the passive avoidance test, the control group which were injected with TMT showed a markedly lower latency time than the non-treated normal group (P < 0.05). However, treatment of Squid-PS significantly recovered the impairment of memory compared to the control group (P < 0.05). Consistent with the behavioral data, Squid-PS significantly alleviated the loss of ChAT immunoreactive neurons in the hippocampal CA3 compared to that of the control group (P < 0.01). Also, Squid-PS significantly increased the AchE positive neurons in the hippocampal CA1 and CA3. In the PET analysis, Squid-PS treatment increased the glucose uptake more than twofold in the frontal lobe and the hippocampus (P < 0.05, resp.). These results suggest that Squid-PS may be useful for improving the cognitive function via regulation of cholinergic enzyme activity and neural activity.

Trimethyltin으로 유도된 기억장애 흰쥐에서 백삼의 신경보호효과

The present study examined the effects of Korean white ginseng (WG, Panax ginseng C. A. Meyer) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered with saline or WG (WG 100 or 300 ㎎/㎏, p.o.) daily for 21 days. The cognitive improving efficacy of WG on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing immunohistochemistries on choline acetyltransferase (ChAT), acetylcholinesterase (AchE), cAMP responsive element binding protein (CREB) and brain derived neurotrophic factor (BDNF). The rats treated with TMT injection (control group) showed impaired learning and memory of the tasks, but the rats treated with TMT injection and WG administration produced significant improvement of the escape latency to find the platform in the Morris water maze at the 2nd and 4th days compared to that of the control group. In the retention test, the WG 100 and WG 300 groups showed significantly increased crossing number around the platform compared to that of the control group (p<0.001). Consistently with the behavioral data, result of immunohistochemistry analysis showed that WG 100 ㎎/㎏ significantly alleviated the loss of BDNF-ir neurons in the hippocampus compared to that of the control group (p<0.01). Also, treatment with WG has a trend to be increased the cholinergic neurons in the hippocampal CA1 and CA3 areas as compared to that of the control group. These results suggest that WG may be useful for improving the cognitive function via regulation of neurotrophic activity.

Tremella fuciformis enhances the neurite outgrowth of PC12 cells and restores trimethyltin-induced impairment of memory in rats via activation of CREB transcription and cholinergic systems

The present study examined the effects of Tremella fuciformis (TF) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered saline or TF (TF 25, 50, 100mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of TF on the amnesic rats, which was induced by TMT, was investigated by assessing the Morris water maze test and by performing Choline acetyltransferase (ChAT) and cAMP responsive element binding protein (CREB) immunohistochemistry. In order to confirm the underlying mechanisms of the memory enhancing effects of TF, we assessed the neurite outgrowth of PC12 cells. We also administered 18F-fluorodeoxyglucose and performed a PET scan of the frontal lobe.The rats with TMT injection showed impaired learning and memory of the tasks and treatment with TF produced a significant improvement of the escape latency to find the platform in the Morris water maze compared to that of the control group. In the retention test, the TF50 group showed increased time spent around the platform compared to that of the control group. Consistent with the behavioral data, TF50mg/kg significantly alleviated the loss of ChAT-ir neurons in the hippocampus compared to that of the control group. Treatment with TF significantly increased the CREB positive neurons in the hippocampal CA1 area as compared to that of the control group. In addition, TF treatment (50mg/kg) increased the glucose uptake approximately sevenfold in the frontal lobe and it significantly promoted neurite outgrowth of the PC12 cells, as compared to that of the controls.These results suggest that TF may be useful for improving the cognitive function via regulation of the CREB signaling pathway and cholinergic system in the hippocampus.

Comparative Experimental Studies on Spatial Memory and Learning in Rats and Robots

The study of behavioral and neurophysiological mechanisms involved in rat spatial cognition provides a basis for the development of computational models and robotic experimentation of goal-oriented learning tasks. These models and robotics architectures offer neurobiologists and neuroethologists alternative platforms to study, analyze and predict spatial cognition based behaviors. In this paper we present a comparative analysis of spatial cognition in rats and robots by contrasting similar goal-oriented tasks in a cyclical maze, where studies in rat spatial cognition are used to develop computational system-level models of hippocampus and striatum integrating kinesthetic and visual information to produce a cognitive map of the environment and drive robot experimentation. During training, Hebbian learning and reinforcement learning, in the form of Actor-Critic architecture, enable robots to learn the optimal route leading to a goal from a designated fixed location in the maze. During testing, robots exploit maximum expectations of reward stored within the previously acquired cognitive map to reach the goal from different starting positions. A detailed discussion of comparative experiments in rats and robots is presented contrasting learning latency while characterizing behavioral procedures during navigation such as errors associated with the selection of a non-optimal route, body rotations, normalized length of the traveled path, and hesitations. Additionally, we present results from evaluating neural activity in rats through detection of the immediate early gene Arc to verify the engagement of hippocampus and striatum in information processing while solving the cyclical maze task, such as robots use our corresponding models of those neural structures.

Medial prefrontal cortex activity can disrupt the expression of stress response habituation

Recent findings suggest that the expression of hypothalamic–pituitary–adrenal (HPA) axis stress response adaptation in rats depends on top–down neural control. We therefore examined whether the medial prefrontal cortex (mPFC) modulates expression of stress response habituation. We transiently suppressed (muscimol microinfusion) or stimulated (picrotoxin microinfusion) mPFC neural activity in rats and studied the consequence on the first time response to psychological stress (restraint) or separately on the development and expression of habituation to repeated restraint. We monitored both the hormonal (corticosterone) and neural (forebrain c-fos mRNA) response to stress. Inactivation of the mPFC had no effect on the HPA-axis response to first time restraint, however increased mPFC activity attenuated stress-induced HPA-axis activity. In a three day repeated restraint stress regimen, inactivation of the mPFC on days 1 and 2, but not day 3, prevented the expression of HPA-axis hormone response habituation. In these same rats, the mPFC activity on day 3 interfered with the expression of c-fos mRNA habituation selectively within the mPFC, lateral septum and hypothalamic paraventricular nucleus. In contrast, inactivation of the mPFC only on day 3, or on all 3 days did not interfere with the expression of habituation. We conclude that the mPFC can permit or disrupt expression of HPA-axis stress response habituation, and this control depends on alteration of neural activity within select brain regions. A possible implication of these findings is that the dysregulation of PFC activity associated with depression and post-traumatic stress disorder may contribute to impaired expression of stress-response adaptation and consequently exacerbation of those disorders.

Central neural activity in rats with tinnitus evaluated with manganese-enhanced magnetic resonance imaging (MEMRI)

The pathophysiology of tinnitus, the perception of sound in the absence of acoustic stimulation, is largely unknown, although several lines of research implicate long-term neuroplastic loss of inhibition. The evidence to date suggests that the neuroplastic alterations are likely to be found in multiple brain structures. The present study used manganese-enhanced magnetic resonance imaging (MEMRI) to assess the pattern of neural activity in the central auditory pathway of rats with psychophysical evidence of chronic acoustic-exposure-induced tinnitus. Manganese, an activity-dependent paramagnetic contrast agent, accumulates in active neurons through voltage-gated calcium channels, primarily at synapses, and serves as both a structural and functional indicator. Comparison images were obtained from normal subjects exposed to external tinnitus-like sound, and from tinnitus subjects treated with vigabatrin, a GABA agonist shown to eliminate the psychophysical evidence of tinnitus in rats. MEMRI indicated: (1) In rats with evidence of tinnitus, activity was generally elevated in the auditory brainstem, with significant elevation in the cerebellar paraflocculus, the posterior ventral cochlear nucleus, and the inferior colliculus; in general forebrain structures showed decreased activity, although MEMRI may be a less sensitive indicator of forebrain activity than brainstem activity; (2) in normal rats exposed to a tinnitus-like sound, a similar pattern of elevated brainstem activity and decreased forebrain activity was evident, with the notable exception of the paraflocculus, where artificial tinnitus had no effect and (3) vigabatrin, decreased brainstem activity to control levels, in rats with prior evidence of tinnitus, and decreased forebrain activity to below control levels. It was concluded that chronic tinnitus in rats is associated with focal activity elevation in the auditory brainstem and increased activity in the paraflocculus that may be unique to tinnitus.

A bipolar electrode for peripheral nerve stimulation

The construction of a bipolar electrode for the stimulation of peripheral nerves is described. The electrode was designed for acute stimued in which the effects of peripheral nerve stimulation on central neural activity in rats were determined. Since the electrode can be secured into a fixed position, neural recordings can be made during the stimulation of various visceral nerves and the electrode can be easily adapted for chronic behavioral studies.