Context contributes to multiple aspects of human episodic memory including segmentation and retrieval. The present studies tested if, in adult male and female mice, context influences the encoding of odors encountered in a single unsupervised sampling session of the type used for the routine acquisition of episodic memories. The three paradigms used differed in complexity (single vs.
View Article and Find Full Text PDFHumans routinely use past experience with complexity to deal with novel, challenging circumstances. This fundamental aspect of real-world behavior has received surprisingly little attention in animal studies, and the underlying brain mechanisms are unknown. The present experiments tested for transfer from past experience in rats and then used quantitative imaging to localize synaptic modifications in hippocampus.
View Article and Find Full Text PDFEndocannabinoids (ECBs) depress transmitter release at sites throughout the brain. Here, we describe another form of ECB signaling that triggers a novel form of long-term potentiation (LTP) localized to the lateral perforant path (LPP) which conveys semantic information from cortex to hippocampus. Two cannabinoid CB1 receptor (CB1R) signaling cascades were identified in hippocampus.
View Article and Find Full Text PDFThe endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), a key modulator of synaptic transmission in mammalian brain, is produced in dendritic spines and then crosses the synaptic junction to depress neurotransmitter release. Here we report that 2-AG-dependent retrograde signaling also mediates an enduring enhancement of glutamate release, as assessed with independent tests, in the lateral perforant path (LPP), one of two cortical inputs to the granule cells of the dentate gyrus. Induction of this form of long-term potentiation (LTP) involved two types of glutamate receptors, changes in postsynaptic calcium, and the postsynaptic enzyme that synthesizes 2-AG.
View Article and Find Full Text PDFUnlabelled: Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months.
View Article and Find Full Text PDFRecent work showed that unsupervised learning of a complex environment activates synaptic proteins essential for the stabilization of long-term potentiation (LTP). The present study used automated methods to construct maps of excitatory synapses associated with high concentrations of one of these LTP-related proteins [CaMKII phosphorylated at T286/287, (pCaMKII)]. Labeling patterns across 42 sampling zones covering entire cross sections through rostral hippocampus were assessed for two groups of rats that explored a novel two-room arena for 30 min, with or without a response contingency involving mildly aversive cues.
View Article and Find Full Text PDFWhether drugs that enhance cognition in healthy individuals will appear in the near future has become a topic of considerable interest. We address this possibility using a three variable system (psychological effect, neurobiological mechanism, and efficiency vs. capabilities) for classifying candidates.
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