Recognition memory for social and non-social odors: differential effects of neurotoxic lesions to the hippocampus and perirhinal cortex.

The contributions of the hippocampus (HC) and perirhinal cortex (PER) to recognition memory are currently topics of debate in neuroscience. Here we used a rapidly-learned (seconds) spontaneous novel odor recognition paradigm to assess the effects of pre-training N-methyl-D-aspartate lesions to the HC or PER on odor recognition memory. We tested memory for both social and non-social odor stimuli. Social odors were acquired from conspecifics, while non-social odors were household spices. Conspecific odor stimuli are ethologically-relevant and have a high degree of overlapping features compared to non-social household spices. Various retention intervals (5 min, 20 min, 1h, 24h, or 48 h) were used between study and test phases, each with a unique odor pair, to assess changes in novelty preference over time. Consistent with findings in other paradigms, modalities, and species, we found that HC lesions yielded no significant recognition memory deficits. In contrast, PER lesions caused significant deficits for social odor recognition memory at long retention intervals, demonstrating a critical role for PER in long-term memory for social odors. PER lesions had no effect on memory for non-social odors. The results are consistent with a general role for PER in long-term recognition memory for stimuli that have a high degree of overlapping features, which must be distinguished by conjunctive representations.

A neurotoxic regimen of methamphetamine impairs novelty recognition as measured by a social odor-based task.

Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" regimen damages forebrain monoaminergic nerve terminals and produces subsequent cognitive deficits. Here we investigate performance on a social odor-based task, demonstrating enduring mAMPH-induced deficits in recognition memory. Three weeks after a neurotoxic mAMPH regimen, singly-housed male Long-Evans rats had four wooden beads placed in their home cage: three beads containing odors from their home cage (HC beads) and one bead from a cage of a rat not present in the colony room (N1 bead). Exploration times for each bead were recorded during three 1-min habituation trials separated by 1-min intertrial intervals. Twenty-four hours later, a 1-min memory test was conducted, in which animals were presented with two HC beads, one N1 bead, and one bead from another novel animal (N2). Saline- and mAMPH-treated rats showed similar, progressive decreases in exploration time for the N1 bead during the habituation trials, indicating equivalent short-term olfactory habituation to the novel odor. By contrast, during the subsequent memory test, saline-treated rats showed a strong preference for the N2 bead over the N1 bead while mAMPH-treated rats showed no preference. The use of the rats' primary sensory modality (olfaction) coupled with the social significance (from conspecifics) of the odors produces strong, long-lasting memories. Our results show that prior treatment with a neurotoxic regimen of mAMPH impairs long-term memory for the previously experienced odors. As compared with previously employed object recognition tasks, this test may be advantageous for investigating mAMPH-induced memory impairments in rodents.

ß-Amyloid impairs axonal BDNF retrograde trafficking.

The neurotrophin, brain-derived neurotrophic factor (BDNF), is essential for synaptic function, plasticity and neuronal survival. At the axon terminal, when BDNF binds to its receptor, tropomyosin-related kinase B (TrkB), the signal is propagated along the axon to the cell body, via retrograde transport, regulating gene expression and neuronal function. Alzheimer disease (AD) is characterized by early impairments in synaptic function that may result in part from neurotrophin signaling deficits. Growing evidence suggests that soluble ß-amyloid (Aß) assemblies cause synaptic dysfunction by disrupting both neurotransmitter and neurotrophin signaling. Utilizing a novel microfluidic culture chamber, we demonstrate a BDNF retrograde signaling deficit in AD transgenic mouse neurons (Tg2576) that can be reversed by γ-secretase inhibitors. Using BDNF-GFP, we show that BDNF-mediated TrkB retrograde trafficking is impaired in Tg2576 axons. Furthermore, Aß oligomers alone impair BDNF retrograde transport. Thus, Aß reduces BDNF signaling by impairing axonal transport and this may underlie the synaptic dysfunction observed in AD.

Alcohol-induced retrograde memory impairment in rats: prevention by caffeine.

RATIONALE: Ethanol and caffeine are two of the most widely consumed drugs in the world, often used in the same setting. Animal models may help to understand the conditions under which incidental memories formed just before ethanol intoxication might be lost or become difficult to retrieve. OBJECTIVES: Ethanol-induced retrograde amnesia was investigated using a new odor-recognition test. MATERIALS AND METHODS: Rats thoroughly explored a wood bead taken from the cage of another rat, and habituated to this novel odor (N1) over three trials. Immediately following habituation, rats received saline, 25 mg/kg pentylenetetrazol (a seizure-producing agent known to cause retrograde amnesia) to validate the test, 1.0 g/kg ethanol, or 3.0 g/kg ethanol. The next day, they were presented again with N1 and also a bead from a new rat's cage (N2). RESULTS: Rats receiving saline or the lower dose of ethanol showed overnight memory for N1, indicated by preferential exploration of N2 over N1. Rats receiving pentylenetetrazol or the higher dose of ethanol appeared not to remember N1, in that they showed equal exploration of N1 and N2. Caffeine (5 mg/kg), delivered either 1 h after the higher dose of ethanol or 20 min prior to habituation to N1, negated ethanol-induced impairment of memory for N1. A combination of a phosphodiesterase-5 inhibitor and an adenosine A(2A) antagonist, mimicking two major mechanisms of action of caffeine, likewise prevented the memory impairment, though either drug alone had no such effect. Binge alcohol can induce retrograde, caffeine-reversible disruption of social odor memory storage or recall.