The perirhinal cortex (PER) is known to process object information, whereas the rodent postrhinal cortex (POR), homolog to the parahippocampal cortex in primates, is thought to process spatial information. A number of studies, however, provide evidence that both areas are involved in processing contextual information. In this study, we tested the hypothesis that the rat POR relies on object information received from the PER to form complex representations of context. Using three fear-conditioning (FC) paradigms (signaled, unsignaled, and renewal) and two context-guided object recognition tasks (with 3D and 2D objects), we examined the effects of crossed excitotoxic lesions to the POR and the contralateral PER. Performance of rats with crossed lesions was compared with that of rats with ipsilateral POR plus PER lesions and sham-operated rats. We found that rats with contralateral PER-POR lesions were impaired in object-context recognition but not in contextual FC. Therefore, interaction between the POR and PER is necessary for context-guided exploratory behavior but not for associating fear with context. Our results provide evidence for the hypothesis that the POR relies on object and pattern information from the PER to encode representations of context. The association of fear with a context, however, may be supported by alternate cortical and/or subcortical pathways when PER-POR interaction is not available. Our results suggest that contextual FC may represent a special case of context-guided behavior. Representations of context are important for perception, memory, decision making, and other cognitive processes. Moreover, there is extensive evidence that the use of contextual representations to guide appropriate behavior is disrupted in neuropsychiatric and neurological disorders including developmental disorders, schizophrenia, affective disorders, and Alzheimer's disease. Many of these disorders are accompanied by changes in parahippocampal and hippocampal structures. Understanding how context is represented in the brain and how parahippocampal structures are involved will enhance our understanding and treatment of the cognitive and behavioral symptoms associated with neurological disorders and neuropsychiatric disease.

Intermittent hypoxia (IH), a characteristic of sleep apnea, was modeled in Fischer Brown Norway rats (10 h/day for 7 days) followed by cognitive testing in an attentional set-shifting task. The ability to shift attention from one sensory modality (e.g., odor) to another (e.g., digging medium) was impaired, a finding that could not be attributed to deficits in attention, discrimination, learning, or motor performance. Instead, the deficit is likely to reflect impaired allocation of attentional resources of the working memory system. Keywords attention; hypoxia; sleep apnea syndromes; discrimination learning; animal models Intermittent hypoxia (IH) and sleep fragmentation are primary characteristics of the sleep apnea syndromes. Adult patients with sleep apnea typically exhibit excessive daytime sleepiness, mood disturbances, and impaired cognition (Roehrs et al., 1995). Evidence suggests that both IH (Row, 2007) and sleep fragmentation (Thomas et al., 2005) may contribute significantly to the observed cognitive deficits. Impaired memory has been observed in humans diagnosed with sleep apnea (Bedard et al., 1991), as well as in laboratory rats exposed to IH to model sleep apnea (Gozal, Daniel, and Dohanich, 2001). While spatial memory deficits in rodents have been repeatedly observed following IH (See Row, 2007 for a review), fewer attempts have been made to model the deficits in executive functioning commonly seen in apneic patients.In the present study, laboratory rats were tested in an attentional set-shifting task following one week (10 h/day for 7 days) of exposure to IH. The task used here was developed by Birrell © 2010 Elsevier B.V. All rights reserved. *1 Institution where work was performed.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The PFC is well known to play a central role in "executive functioning," a term which refers here to the parceling out of attentional resources in response to changing environmental demands by components of the working memory system, which holds information on-line for immediate use (Baddeley, 1992). Studies employing positron emission tomography (PET) have shown that extradimensional shifting activates the dorsolateral PFC in humans (Rogers et al., 2000). Furthermore, humans who have sustained damage to the PFC exhibit impaired performance on problem solving tasks that require the subject to shift attention from one rule to another (Owen et al., 1991). In rats, lesion studies have demonstrated a key role for the medial PFC in attentional set-shifting (Birrell and Brown, 2000). The present study evaluated the performance o...

Although numerous experimental investigations have evaluated the neurobehavioral effects of either short periods of total sleep deprivation or selective rapid eye movement sleep deprivation, few studies have examined the effects of chronic sleep restriction (CSR). Long-Evans rats were deprived of sleep by the automated movement of activity wheels for 18 h/day for 5 consecutive days from 16:00 to 10:00 h, and were allowed 6 h/day of sleep opportunity (10:00–16:00 h; lights on from 10:00 to 22:00 h). Activity wheels were intermittently activated on a 3 s on : 12 s off schedule for the CSR condition, whereas a schedule of 36 min of continuous wheel movement in every 3 h was used for a cage movement control condition. A cross-over design was used with rats serving in both the CSR and the movement control conditions with 2 days of rest between conditions. Water maze acquisition training occurred at 16:00 h immediately after the 6-h sleep opportunity on each of the first 4 days, followed by a probe trial on day 5 to assess spatial memory recall. Although the rate of learning/acquisition was not affected by the daily 18 h of CSR, the day 5 recall of the platform location was impaired on three different probe trial measures. Thus, CSR impaired spatial memory, but did not affect the rate of learning/acquisition in the water maze.

Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects. For example, animals and humans with perirhinal damage are unable to distinguish familiar from novel objects in recognition memory tasks. In the normal brain, perirhinal neurons respond to novelty and familiarity by increasing or decreasing firing rates. Recent work also implicates oscillatory activity in the low-beta and low-gamma frequency bands in sensory detection, perception, and recognition. Using optogenetic methods in a spontaneous object exploration (SOR) task, we altered recognition memory performance in rats. In the SOR task, normal rats preferentially explore novel images over familiar ones. We modulated exploratory behavior in this task by optically stimulating channelrhodopsin-expressing perirhinal neurons at various frequencies while rats looked at novel or familiar 2D images. Stimulation at 30-40 Hz during looking caused rats to treat a familiar image as if it were novel by increasing time looking at the image. Stimulation at 30-40 Hz was not effective in increasing exploration of novel images. Stimulation at 10-15 Hz caused animals to treat a novel image as familiar by decreasing time looking at the image, but did not affect looking times for images that were already familiar. We conclude that optical stimulation of PER at different frequencies can alter visual recognition memory bidirectionally.

SummaryLearning to perceptually discriminate between chemical signals in the environment (olfactory perceptual learning [OPL]) is critical for survival. Multiple mechanisms have been implicated in OPL, including modulation of neurogenesis and manipulation of cholinergic activity. However, whether these represent distinct processes regulating OPL or if cholinergic effects on OPL depend upon neurogenesis has remained an unresolved question. Using a combination of pharmacological and optogenetic approaches, cholinergic activity was shown to be both necessary and sufficient to drive OPL, and this process was dependent on the presence of newly born cells in the olfactory bulb (OB). This study is the first to directly demonstrate that cholinergic effects on OPL require adult OB neurogenesis.