Publications by authors named "Christopher J Macdonald"

There is considerable evidence for hippocampal time cells that briefly activate in succession to represent the temporal structure of memories. Previous studies have shown that time cells can be disrupted while leaving place cells intact, indicating that spatial and temporal information can be coded in parallel. However, the circuits in which spatial and temporal information are coded have not been clearly identified.

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Unlabelled: The purpose of this monitoring study was to investigate how alterations in training affect changes in force-related characteristics and weightlifting performance.

Subjects: Seven competitive weightlifters participated in the study.

Methods: The weightlifters performed a block style periodized plan across 20 weeks.

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The entorhinal cortex (EC)-hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence of past events. Although there has been significant progress toward understanding the neural circuits underlying the spatial dimension of episodic memory, the relevant circuits subserving the temporal dimension are just beginning to be understood. In this review, we examine the evidence concerning the role of the EC in associating events separated by time--or temporal associative learning--with emphasis on the function of persistent activity in the medial entorhinal cortex layer III (MECIII) and their direct inputs into the CA1 region of HPC.

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Stress is considered a potent environmental risk factor for many behavioural abnormalities, including anxiety and mood disorders. Animal models can exhibit limited but quantifiable behavioural impairments resulting from chronic stress, including deficits in motivation, abnormal responses to behavioural challenges, and anhedonia. The hippocampus is thought to negatively regulate the stress response and to mediate various cognitive and mnemonic aspects of stress-induced impairments, although the neuronal underpinnings sufficient to support behavioural improvements are largely unknown.

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A recent report estimates that the number of simultaneously recorded neurons is growing exponentially. A commonly employed statistical paradigm using discrete-time point process models of neural activity involves the computation of a maximum-likelihood estimate. The time to computate this estimate, per neuron, is proportional to the number of bins in a finely spaced discretization of time.

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The medial temporal lobe (MTL) is believed to support episodic memory, vivid recollection of a specific event situated in a particular place at a particular time. There is ample neurophysiological evidence that the MTL computes location in allocentric space and more recent evidence that the MTL also codes for time. Space and time represent a similar computational challenge; both are variables that cannot be simply calculated from the immediately available sensory information.

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Psychologists have long distinguished between prospective and retrospective timing to highlight the difference between our sense of duration during an experience in passing and our sense of duration in hindsight. Humans and other animals use prospective timing in the seconds-to-minutes range in order to learn durations, and can organize their behaviour based upon this knowledge when they know that duration information will be important ahead of time. By contrast, when durations are estimated after the fact, thus precluding the subject from consciously attending to temporal information, duration information must be extracted from other memory representations.

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Previous studies have revealed the existence of hippocampal "time cells," principal neurons in CA1 that fire at specific moments in temporally organized experiences. However, in all these studies, animals were in motion; and so, temporal modulation might be due, at least in part, to concurrent or planned movement through space or self-generated movement (path integration). Here the activity of hippocampal CA1 neurons was recorded in head-fixed and immobile rats while they remembered odor stimuli across a delay period.

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Optic neuritis can be defined as typical (associated with multiple sclerosis, improving independent of steroid treatment), or atypical (not associated with multiple sclerosis, steroid-dependent improvement). Causes of atypical optic neuritis include connective tissue diseases (eg, lupus), vasculitis, sarcoidosis, or neuromyelitis optica. In this manuscript, updated treatment options for both typical and atypical optic neuritis are reviewed.

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The gustatory cortex (GC) is important for perceiving the intensity of tastants but it remains unclear as to how single neurons in the region carry out this function. Previous studies have shown that taste-evoked activity from single neurons in GC can be correlated or anticorrelated with tastant concentration, yet whether one or both neural responses signal intensity is poorly characterized because animals from these studies were not trained to report the intensity of the concentration that they tasted. To address this issue, we designed a two-alternative forced choice (2-AFC) task in which freely licking rats distinguished among concentrations of NaCl and recorded from ensembles of neurons in the GC.

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Time-based decision-making in peak-interval timing procedures involves the setting of response thresholds for the initiation ("Start") and termination ("Stop") of a response sequence that is centered on a target duration. Using intracerebral infusions of the protein synthesis inhibitor anisomycin, we report that the acquisition of the "Start" response depends on normal functioning (including protein synthesis) in the dorsal striatum (DS), but not the ventral striatum (VS). Conversely, disruption of the VS, but not the DS, impairs the acquisition of the "Stop" response.

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A method is presented capable of disambiguating the relative influence of statistical covariates upon neural spiking activity. The method, an extension of the generalized linear model (GLM) methodology introduced in Truccolo et al. (2005) to analyze neural spiking data, exploits projection operations motivated by a geometry present in the Fisher information of the GLM maximum likelihood parameter estimator.

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Complex training (CT; alternating between heavy and lighter load resistance exercises with similar movement patterns within an exercise session) is a form of training that may potentially bring about a state of postactivation potentiation, resulting in increased dynamic power (Pmax) and rate of force development during the lighter load exercise. Such a method may be more effective than either modality, independently for developing strength. The purpose of this research was to compare the effects of resistance training (RT), plyometric training (PT), and CT on lower body strength and anthropometrics.

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The hippocampus is critical to remembering the flow of events in distinct experiences and, in doing so, bridges temporal gaps between discontiguous events. Here, we report a robust hippocampal representation of sequence memories, highlighted by "time cells" that encode successive moments during an empty temporal gap between the key events, while also encoding location and ongoing behavior. Furthermore, just as most place cells "remap" when a salient spatial cue is altered, most time cells form qualitatively different representations ("retime") when the main temporal parameter is altered.

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The dopamine transporter (DAT) is the major regulator of the spatial and temporal resolution of dopaminergic neurotransmission in the brain. Hyperdopaminergic mice with DAT gene deletions were evaluated for their ability to perform duration discriminations in the seconds-to-minutes range. DAT -/- mice were unable to demonstrate temporal control of behavior in either fixed-interval or peak-interval timing procedures, whereas DAT +/- mice were similar to DAT +/+ mice under normal conditions.

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Much remains to be understood about the differential contributions from primary and secondary sensory cortices to sensory-guided decision making. To address this issue we simultaneously recorded activity from neuronal ensembles in primary [gustatory cortex GC)] and secondary gustatory [orbitofrontal cortex (OFC)] cortices while rats made a taste-guided decision between two response alternatives. We found that before animals commenced a response guided by a tastant cue, GC ensembles contained more information than OFC about the response alternative about to be selected.

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Nitric oxide (NO)-donating non-steroidal anti-inflammatory drugs (NSAIDs) represent a promising new class of drugs developed to provide a safer alternative than their conventional NSAID counterparts in chemoprevention. We tested the effects of NO-aspirin 2 on Phase I and Phase II carcinogen-metabolizing enzymes. In HepG2 human hepatoma cells and in LS180 colonic adenocarcinoma cells, NO-aspirin 2 inhibited 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD)-induced cytochrome P450 (CYP) enzyme activity and CYP1A1 and CYP1A2 mRNA expression.

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Purpose: Nonsteroidal anti-inflammatory drugs (NSAID) are promising chemopreventive agents against colon and other cancers. However, the molecular basis mediated by NSAIDs for chemoprevention has not been fully elucidated. Environmental carcinogens induce DNA mutation and cellular transformation; therefore, we examined the effect of NSAIDs on carcinogenesis mediated by the aryl hydrocarbon receptor signaling pathway.

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Choline availability in the maternal diet has a lasting effect on brain and behavior of the offspring. To further delineate the impact of early nutritional status, we examined effects of prenatal-choline supplementation on timing, emotion, and memory performance of adult male and female rats. Rats that were given sufficient choline (CON: 1.

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Sulindac is a nonsteroidal antiinflammatory drug that has been demonstrated to be a potent chemopreventive agent against colorectal cancer in both human and animal models. In vivo, sulindac may be reversibly reduced to the active antiinflammatory compound, sulindac sulfide, or irreversibly oxidized to sulindac sulfone. Sulindac has also been shown to inhibit polycyclic aromatic hydrocarbon (PAH)-induced cancer, but the molecular mechanisms of its antitumor effect remain unclear.

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The cognitive and emotional effects of amygdala or frontal cortex lesions were compared in rats trained to time both a 50-s visual signal paired with food and an embedded 10- or 20-s auditory signal that was paired with either appetitive (food) or aversive (footshock) outcomes. When both auditory and visual signals were paired with food, control and amygdalar-lesioned rats were able to divide attention and to time both signals simultaneously, whereas when the embedded auditory signal was paired with footshock, control rats were impaired in their ability to divide attention and were able to time only one signal at a time. In contrast, amygdalar inactivation blocked this fear-related impairment and allowed rats to time both signals simultaneously, whereas rats with frontal cortex lesions demonstrated sequential processing under all conditions.

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The present study examined the effects of photoperiod on spatial and temporal memory in adult Sprague-Dawley rats that were conceived and reared in different day lengths, i.e., short day (SD-8:16 light/dark) and long day (LD-16:8 light/dark).

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In a series of three experiments, simple reaction time (RT) was characterized with respect to a variable preparatory interval (PI) in order to investigate the relationship between interval timing and RT. In Experiment 1, it was shown that RT decreases as a function of PI and that this effect varies with amount of training. In Experiment 2, RT was shown to increase during probe trials that used a novel 6.

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