Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for…

The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required…

It is well established that fear memory formation requires de novo gene transcription in the amygdala. We provide evidence that epigenetic mechanisms in the form of histone lysine methylation in the lateral amygdala (LA) are regulated by NMDA receptor (NMDAR) signaling and involved in gene transcription changes necessary for fear memory…

Previous research on sensitization in "Aplysia" was based entirely on unnatural noxious stimuli, usually electric shock, until our laboratory found that a natural noxious stimulus, a single sublethal lobster attack, causes short-term sensitization. We here extend that finding by demonstrating that multiple lobster attacks induce…

Modulation of cortical network connectivity is crucial for an adaptive response to experience. In the rat barrel cortex, long-term sensory stimulation induces cortical network modifications and neuronal response changes of which the molecular basis is unknown. Here, we show that long-term somatosensory stimulation by enriched environment…

We investigated the specific role of zinc present in large amounts in the synaptic vesicles of mossy fibers and coreleased with glutamate in the CA3 region. In previous studies, we have shown that blockade of zinc after release has no effect on the consolidation of spatial learning, while zinc is required for the consolidation of contextual fear…

Though much attention has been given to the neural structures that underlie the long-term consolidation of contextual memories, little is known about the mechanisms responsible for the maintenance of memory precision. Here, we demonstrate a rapid time-dependent decline in memory precision in GABA [subscript B(1a)] receptor knockout mice. First, we…

Learning-induced modulation of neuronal intrinsic excitability is a metaplasticity mechanism that can impact the acquisition of new memories. Although the amygdala is important for emotional learning and other behaviors, including fear and anxiety, whether learning alters intrinsic excitability within the amygdala has received very little…

Learning to ignore irrelevant stimuli is essential to achieving efficient and fluid attention, and serves as the complement to increasing attention to relevant stimuli. The different cholinergic (ACh) subsystems within the basal forebrain regulate attention in distinct but complementary ways. ACh projections from the substantia innominata/nucleus…

Memory can be distorted by misleading post-event information. These memory distortions may have serious consequences, for example in eyewitness testimony. Many situations in which memory reports are solicited, and suggestive or misleading information is presented, are highly stressful for the respondent, yet little is known about how stress…

The prelimbic cortex has been implicated in the consolidation of previously learned fear. Herein, we report that temporarily inactivating this medial prefrontal cortex subregion with the GABA [subscript A] agonist muscimol (4.0 nmol in 0.2 µL per hemisphere) was able to equally disrupt 1-, 7-, and 21-d-old contextual fear memories after their…

Numerous studies have suggested a role for ubiquitin-proteasome-mediated protein degradation in learning-dependent synaptic plasticity; however, very little is known about how protein degradation is regulated at the level of the proteasome during memory formation. The ubiquitin-specific protease 14 (USP14) is a proteasomal deubiquitinating enzyme…

An important cellular mechanism contributing to the strength and duration of memories is activity-dependent alterations in the strength of synaptic connections within the neural circuit encoding the memory. Reversal of the memory is typically correlated with a reversal of the cellular changes to levels expressed prior to the stimulation. Thus, for…

Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging-associated frailty can preclude physical activity. In young sedentary animals, pharmacological activation of AMP-activated protein kinase (AMPK), a transcriptional regulator important for muscle physiology, enhanced…

Many insignificant events in our daily life are forgotten quickly but can be remembered for longer when other memory-modulating events occur before or after them. This phenomenon has been investigated in animal models in a protocol in which weak memories persist longer if exploration in a novel context is introduced around the time of memory…