Batty ER, Hoban L, Spetch ML, Dickson CT
Behav. Processes 2009 Nov;82(3):327-34
Over the past 20 years, a great deal of research has examined how different animals can use the geometric properties of the environment to determine their heading. Less well studied is how rats use the geometric properties of an environment to navigate, or determine the location, when it is not necessary to establish heading. Specifically, it is unclear to what extent rats still rely on geometric cues when they are not disoriented. In the current study, rats were trained to find food in one corner of a rectangular environment under either oriented or disoriented conditions. Probe tests placed geometric, featural and orientation cues in conflict. Results showed that featural cues exerted little control over the rats’ search preferences. All rats, whether trained while oriented or trained while disoriented, used geometric cues when these were the only cues available. Rats trained in the disoriented condition preferred geometric cues to orientation cues, whereas rats trained in the oriented condition showed more equal preference for orientation and geometric cues.
Nazer F, Dickson CT
J. Neurophysiol. 2009 Sep;102(3):1880-9
In mesial temporal lobe (MTL) epilepsy, which typically involves the hippocampus (HPC), epileptiform events are enhanced during slow wave sleep (SWS). It remains unclear how and why the electroencephalographic (EEG) states that constitute SWS might predispose the HPC to this type of pathological activity. Recently our laboratory has described a novel state of deactivated hippocampal EEG activity that occurs during both SWS and urethan anesthesia: the slow oscillation (SO). This activity is characterized by a high-amplitude approximately 1-Hz signal, high synchrony within the hippocampus, and a dynamic coordination with neocortical SO. To assess how this activity state might influence epileptiform discharges, we studied the properties of stimulation-evoked and spontaneous epileptiform events elicited in the HPC of urethan-anesthetized rats. We compared those elicited during the SO to those occurring during the theta rhythm. The average duration but not the amplitude of evoked afterdischarges (ADs) was consistently larger during the SO. In addition, spontaneous epileptiform events were more frequent and of higher amplitude during the SO. Last, the bilateral propagation of both ADs and spontaneous events in the hippocampus was enhanced during the SO. These results imply that the threshold for the generation and propagation of epileptiform activity in the hippocampus is lowered during the SO and that this state may be a seed for the initiation, maintenance, and generalization of MTL epilepsy. Further examination of the pathophysiology of sleep-epilepsy interactions in the HPC will be of benefit for an understanding of the mechanisms, prognosis, and therapy for this form of epilepsy.
Whitten TA, Martz LJ, Guico A, Gervais N, Dickson CT
J. Neurophysiol. 2009 Sep;102(3):1647-56
During sleep, warm-blooded animals exhibit cyclic alternations between rapid-eye-movement (REM) and nonrapid-eye-movement (non-REM) states, characterized by distinct patterns of brain activity apparent in electroencephalographic (EEG) recordings coupled with corresponding changes in physiological measures, including body temperature. Recently we have shown that urethane-anesthetized rats display cyclic alternations between an activated state and a deactivated state that are highly similar in both EEG and physiological characteristics to REM and non-REM sleep states, respectively. Here, using intracranial local field potential recordings from urethane-anesthetized rats, we show that brain-state alternations were correlated to core temperature fluctuations induced using a feedback-controlled heating system. Activated (REM-like) states predominated during the rising phase of the temperature cycle, whereas deactivated (non-REM-like) states predominated during the falling phase. Brain-state alternations persisted following the elimination of core temperature fluctuations by the use of a constant heating protocol, but the timing and rhythmicity of state alternations were altered. In contrast, thermal fluctuations applied to the ventral surface (and especially the scrotum) of rats in the absence or independently of core temperature fluctuations appeared to induce brain-state alternations. Heating brought about activated patterns, whereas cooling produced deactivated patterns. This shows that although alternations of sleeplike brain states under urethane anesthesia can be independent of imposed temperature variations, they can also be entrained through the activation of peripheral thermoreceptors. Overall, these results imply that brain state and bodily metabolism are highly related during unconsciousness and that the brain mechanisms underlying sleep cycling and thermoregulation likely represent independent, yet coupled oscillators.
Engin E, Treit D, Dickson CT
Neuroscience 2009 Jun;161(2):359-69
Ketamine, a dissociative anesthetic agent, appears to have rapid antidepressant effects at sub-anesthetic doses in clinically depressed patients. Although promising, these results need to be replicated in double-blind placebo-controlled studies, a strategy thwarted by the psychoactive effects of ketamine, which are obvious to both patients and clinicians. Alternatively, demonstrations of the psychotherapeutic effects of ketamine in animal models are also complicated by ketamine’s side-effects on general activity, which have not been routinely measured or taken into account in experimental studies. In this study we found that ketamine decreased “behavioral despair” in the forced swim test, a widely used rats model of antidepressant drug action. This effect was not confounded by side-effects on general activity, and was comparable to that of a standard antidepressant drug, fluoxetine. Interestingly, ketamine also produced anxiolytic-like effects in the elevated-plus-maze. Importantly, the effective dose of ketamine in the plus-maze did not affect general locomotion measures, in either the plus-maze or in the open field test. While the selective N-methyl-d-aspartic acid (NMDA) receptor antagonist MK-801 also produced antidepressant-like and anxiolytic-like effects, these were mostly confounded by changes in general activity. Finally, in a neurophysiological model of anxiolytic drug action, ketamine reduced the frequency of reticularly-activated theta oscillations in the hippocampus, similar to the proven anxiolytic drug diazepam. This particular neurophysiological signature is common to all known classes of anxiolytic drugs (i.e. benzodiazepines, 5-HT1A agonists, antidepressants) and provides strong converging evidence for the anxiolytic-like effects of ketamine. Further studies are needed to understand the underlying pharmacological mechanisms of ketamine’s effects in these experiments, since it is not clear they were mimicked by the selective NMDA antagonist MK-801.