Broadly tuned and respiration-independent inhibition in the olfactory bulb of awake mice.

Olfactory representations are shaped by brain state and respiration. The interaction and circuit substrates of these influences are unclear. Granule cells (GCs) in the main olfactory bulb (MOB) are presumed to sculpt activity reaching the cortex via inhibition of mitral/tufted cells (MTs). GCs potentially make ensemble activity more sparse by facilitating lateral inhibition among MTs and/or enforce temporally precise activity locked to breathing. Yet the selectivity and temporal structure of wakeful GC activity are unknown. We recorded GCs in the MOB of anesthetized and awake mice and identified state-dependent features of odor coding and temporal patterning. Under anesthesia, GCs were sparsely active and strongly and synchronously coupled to respiration. Upon waking, GCs desynchronized, broadened their tuning and largely fired independently from respiration. Thus, during wakefulness, GCs exhibited stronger odor responses with less temporal structure. We propose that during wakefulness GCs may shape MT odor responses through broadened lateral interactions rather than respiratory synchronization.

Prenatal exposure to a viral mimetic alters behavioural flexibility in male, but not female, rats.

Current understanding of the etiology of neurodevelopmental disorders is limited; however, recent epidemiological studies demonstrate a strong correlation between prenatal infection during pregnancy and the development of schizophrenia in adult offspring. In particular, schizophrenia patients subjected to prenatal infection exhibit impairments in executive functions greater than schizophrenia patients not exposed to an infection while in utero. Acute prenatal treatment of rodents with the viral mimetic polyinosinic-polycytidylic acid (PolyI:C) induces behavioural and neuropathological alterations in the adult offspring similar to schizophrenia. However, impairments on tasks of executive function that involve the prefrontal cortex (PFC) have been rarely examined for the prenatal infection model. Hence, we investigated the effects of acute prenatal injection of PolyI:C (4.0 mg/kg, i.v., gestational day 15) on strategy set-shifting and reversal learning in an operant-based task. Our results show male, but not female, PolyI:C-treated adult offspring require more trials to reach criterion and perseverate during set-shifting. An opposite pattern was seen on the reversal day where the PolyI:C-treated male rats made fewer regressive errors. Females took more pre-training days and were slower to respond during the trials when compared to males regardless of prenatal treatment. The present findings validate the utility of the prenatal infection model for examining alterations of executive function, one of the most prominent cognitive symptoms of schizophrenia.

AMPA receptor endocytosis in rat perirhinal cortex underlies retrieval of object memory.

Mechanisms consistent with long-term depression in the perirhinal cortex (PRh) play a fundamental role in object recognition memory; however, whether AMPA receptor endocytosis is involved in distinct phases of recognition memory is not known. To address this question, we used local PRh infusions of the cell membrane-permeable Tat-GluA2(3Y) interference peptide or a scrambled control to block the endocytosis of AMPA receptors during the encoding, consolidation, or retrieval phase of object recognition memory. Tat-GluA2(3Y) infusion before the encoding and consolidation phases did not alter recognition memory. In contrast, Tat-GluA2(3Y) infusion prior to the retrieval phase disrupted object recognition memory. The present results indicate a distinct role for AMPA receptor endocytosis in the retrieval of visual recognition memory.

Converging effects of acute stress on spatial and recognition memory in rodents: a review of recent behavioural and pharmacological findings.

The heterogeneous effects of acute stress on learning and memory depend on numerous parameters related to the stressor, the time the stressor is experienced, and the nature of the stimuli or task examined. In the present review, we systematically summarize the rodent literature examining the effects of acute extrinsic stress on spatial and recognition memory. Converging evidence from a number of behavioural tasks suggests acute stress disrupts the retrieval of spatial and recognition memory regardless of whether the stress is experienced before or after learning. Few studies have attempted to discern whether these effects are due to specific failures in consolidation or retrieval of task relevant information. Recent studies demonstrate that diverse mechanisms related to activation of the hypothalamic-pituitary-adrenal axis and alterations in glutamatergic synaptic plasticity mediate the effects of acute stress on spatial and recognition memory. Taken together, these findings have significantly advanced our understanding of the neural mechanisms mediating learning and memory and may stimulate the search for novel therapeutics to treat stress-related psychiatric disorders.

Acute stress disrupts paired pulse facilitation and long-term potentiation in rat dorsal hippocampus through activation of glucocorticoid receptors.

Cognitive functions such as learning and memory are widely believed to depend on patterns of short- and long-term synaptic plasticity. Factors, such as acute stress, which affect learning and memory, may do so by altering patterns of synaptic plasticity in distinct neural circuits. Numerous studies have examined the effects of acute stress on long-term synaptic plasticity; however, few have examined its influence on short-term plasticity. The present experiments directly assessed the effects of acute stress on short-term synaptic plasticity as measured by paired pulse facilitation (PPF) of excitatory postsynaptic potentials recorded from rat dorsal hippocampus (dHip) in vivo. Long-term potentiation (LTP) was also examined. Acute stress induced by exposure to an elevated platform impaired PPF and LTP in the dHip. Pretreatment of rats exposed to stress with mifepristone (RU38486; 10 mg kg⁻¹) blocked the stress-induced impairment of both PPF and LTP. These data demonstrate that activation of glucocorticoid receptors during acute stress disrupts normal patterns of both PPF and LTP in the dHip.

Effects of acute stress and GluN2B-containing NMDA receptor antagonism on object and object-place recognition memory.

The mechanisms underlying the complex effects of acute stress on memory are incompletely understood. Previous work suggests that the activation of N-methyl-d-aspartate (NMDA) receptors specifically containing GluN2B subunits may underlie the disruptions in spatial memory retrieval caused by acute stress (Wong et al., 2007 PNAS 104:11471). The present experiments were designed to assess whether a similar mechanism is involved in recognition memory. Recognition memory retrieval was assessed in Sprague-Dawley rats using an object recognition test and an object-place recognition test, both of which rely on patterns of spontaneous exploration. Exposure to acute stress for 30 min immediately before the test phase of either test disrupted memory retrieval. Administration of the GluN2B-selective antagonist Ro25-6981 (6 mg/kg; i.p.) enhanced memory in the object recognition test regardless of whether animals were exposed to acute stress. In the object-place test, Ro25-6981 had no effect on memory retrieval in the absence of stress but promoted memory following acute stress. These data highlight the specific contributions made by GluN2B-containing NMDA receptors to recognition memory for different types of stimuli.