Experimental evidence suggests that the hippocampal theta rhythm plays a critical role in learning. Previous studies have shown long-term potentiation (LTP) to be preferentially induced with stimulation on the peak of local theta rhythm in region CA1 in anesthetized rats and with stimulation of the perforant path at the peak of theta in both anesthetized and behaving animals. We set out to determine the effects of tetanic burst stimulation in stratum radiatum of region CA1 in awake behaving animals, delivered during either the peak or the trough of the theta rhythm in the EEG. Bursts delivered to the peak resulted in an increase of 17.9 +/- 0.94% in potential slope. When identical stimulation bursts were delivered to the trough of local theta waves, the potential slope decreased 12.9 +/- 1.03%. This is the first report of LTP being preferentially induced at the peak of local theta rhythm in behaving animals in region CA1 and that LTD was found in response to tetanic stimulation at the trough of the local theta wave. The results are discussed within the framework of a recent theory that proposes that the theta rhythm sets the dynamics for alternating phases of encoding and retrieval (Hasselmo et al., 20021).

These experiments examine changes in theta power as measured by wavelet analysis in five rats performing a conditional visual discrimination task and a simple running task. In the conditional task, rats were trained to press one lever to initiate a trial and then to press one of two choice levers, each corresponding to one of two cue lights. Analysis of theta power in this operant task found a large decrease in theta power during the choice bar presses, in contrast to the increase in theta power during trial initiation bar presses. This result seems to stand counter to results that propose consistent relationships between motor actions and theta power (Vanderwolf, EEG Clin Neurophys 26:407-418, 1969), as well as studies suggesting that the lack of bar-press theta is the result of habituation. However, these data can be seen as being in broad agreement with the theoretical framework of sensorimotor integration (Bland and Oddie, Behav Brain Res 127:119-136, 2001). To investigate further the power of theta observed at the termination of type 1 motor activity, a runway task was devised in which rats ran back and forth between two ends of a linear track, one of which was always rewarded and the other never rewarded. Theta power decreased sharply 240 ms before movement ended at the rewarded end, but not at the unrewarded end of the track. These data extend the current scope of theory in demonstrating that hippocampal theta activity can end abruptly 200-400 ms prior to the end of type 1 motor movement when approaching the end of a motor sequence.

BackgroundEpidemiologic evidence suggests that chronic stress may alter susceptibility to air pollution. However, persistent spatial confounding between these exposures may limit the utility of epidemiologic methods to disentangle these effects and cannot identify physiologic mechanisms for potential differential susceptibilities.ObjectivesUsing a rat model of social stress, we compared respiratory responses to fine concentrated ambient particles (CAPs) and examined biological markers of inflammation.MethodsTwenty-four 12-week-old male Sprague-Dawley rats were randomly assigned to four groups [stress/CAPs, stress/filtered air (FA), nonstress/CAPs, nonstress/FA]. Stress-group animals were individually introduced into the home cage of a dominant male twice weekly. Blood drawn at sacrifice was analyzed for immune and inflammatory markers. CAPs were generated using the Harvard ambient particle concentrator, which draws real-time urban ambient fine particles, enriching concentrations approximately 30 times. CAPs/FA exposures were delivered in single-animal plethysmographs, 5 hr/day for 10 days, and respiratory function was continuously monitored using a Buxco system.ResultsStressed animals displayed higher average C-reactive protein, tumor necrosis factor-α, and white blood cell counts than did nonstressed animals. Only among stressed animals were CAPs exposures associated with increased respiratory frequency, lower flows, and lower volumes, suggesting a rapid, shallow breathing pattern. Conversely, in animals with elevated CAPs exposures alone, we observed increased inspiratory flows and greater minute volumes (volume of air inhaled or exhaled per minute).ConclusionsCAPs effects on respiratory measures differed significantly, and substantively, by stress group. Higher CAPs exposures were associated with a rapid, shallow breathing pattern only under chronic stress. Blood measures provided evidence of inflammatory responses. Results support epidemiologic findings that chronic stress may alter respiratory response to air pollution and may help elucidate pathways for differential susceptibility.

SummaryPre-treatment with the endocannabinoid-receptor antagonist, SR141716, has been reported to suppress the long-lasting hyperexcitability and increased seizure susceptibility present after 30 min of hyperthermia-induced convulsions in immature rats, an animal model of complex febrile seizures in children, which may be a cause of temporal lobe epilepsy. The present experiments tested the hypothesis that SR141716 suppresses epileptogenesis in the adult kainate model, an animal model of temporal lobe epilepsy. Adult male rats (n=35), implanted for electroencephalogram (EEG) recordings, were treated with kainate. Immediately after the first acute electrographic seizure during kainate-induced status epilepticus, either vehicle or SR141716 (10 mg/kg) was injected intraperitoneal. Chronic video-EEG data were collected for the first 2-week period after kainate-induced status epilepticus. Over half of both the vehicle-and drugtreated animals showed spontaneous recurrent seizures. Similarly, mean seizure frequency was not significantly different for the drug-and vehicle-treated animals during the first 2 weeks (n=9 and 8, respectively). Thus, no significant differences were found between SR141716-treated and control animals during the first 2 weeks of epileptogenesis. These results suggest that the endocannabinoid-receptor antagonist, SR141716, had no detectable effect on the early stages of epileptogenesis in the adult kainate model. Several potential explanations for the differences in the effects of SR141716 in the adult-rat, kainate versus immature-rat, hyperthermia models are discussed.

Inflammatory T cells that are reactive to myelin protein components of the CNS play a critical role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). The authors have previously generated mice that predominantly harbor T cells transgenic for a T-cell receptor (TCR) that is specific to the myelin proteolipid protein (PLP) 139-151 and that spontaneously develop MS-like paralysis. T cells from healthy transgenic mice respond to stimulation with PLP139-151 in a highly specific manner by proliferation and secretion of proinflammatory cytokines such as interleukin (IL)-2 and interferon (INF)-gamma in vitro. To identify druglike compounds that may inhibit inflammatory T-cell responses, the authors have developed a high-throughput screening assay with primary T cells from PLP TCR transgenic mice. They have screened 41,184 small-molecule compounds that follow Lipinski's rules for their inhibitory activity on the proliferation and secretion of proinflammatory cytokines in PLP-reactive T cells. To this end, the screen identified 6 nontoxic compounds with a molecular weight <500 that inhibited inflammatory responses in PLP-reactive T cells in a concentration-dependent fashion. The identified compounds represent valid leads that may be developed into novel therapeutics for MS that could be administered orally.

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