Disruption of Long-Term Depression Potentiates Latent Inhibition: Key Role for Central Nucleus of the Amygdala

Background Latent inhibition (LI) reflects an adaptive form of learning impaired in certain forms of mental illness. Glutamate receptor activity is linked to LI, but the potential role of synaptic plasticity remains unspecified. Methods Accordingly, the present study examined the possible role of long-term depression (LTD) in LI induced by prior exposure of rats to an auditory stimulus used subsequently as a conditional stimulus to signal a pending footshock. We employed 2 mechanistically distinct LTD inhibitors, the Tat-GluA23Y peptide that blocks endocytosis of the GluA2-containing glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, or the selective glutamate n-methyl-d-aspartate receptor 2B antagonist, Ro25-6981, administered prior to the acquisition of 2-way conditioned avoidance with or without tone pre-exposure. Results Systemic LTD blockade with the Tat-GluA23Y peptide strengthened the LI effect by further impairing acquisition of conditioned avoidance in conditional stimulus-preexposed rats compared with normal conditioning in non-preexposed controls. Systemic Ro25-6981 had no significant effects. Brain region–specific microinjections of the Tat-GluA23Y peptide into the nucleus accumbens, medial prefrontal cortex, or central or basolateral amygdala demonstrated that disruption of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor endocytosis in the central amygdala also potentiated the LI effect. Conclusions These data revealed a previously unknown role for central amygdala LTD in LI as a key mediator of cognitive flexibility required to respond to previously irrelevant stimuli that acquire significance through reinforcement. The findings may have relevance both for our mechanistic understanding of LI and its alteration in disease states such as schizophrenia, while further elucidating the role of LTD in learning and memory.

Fruit flies can learn non-elemental olfactory discriminations

Associative learning allows animals to establish links between stimuli based on their concomitance. In the case of Pavlovian conditioning, a single stimulus A (the conditional stimulus, CS) is reinforced unambiguously with an unconditional stimulus (US) eliciting an innate response. This conditioning constitutes an ‘elemental’ association to elicit a learnt response from A + without US presentation after learning. However, associative learning may involve a ‘complex’ CS composed of several components. In that case, the compound may predict a different outcome than the components taken separately, leading to ambiguity and requiring the animal to perform so-called non-elemental discrimination. Here, we focus on such a non-elemental task, the negative patterning (NP) problem, and provide the first evidence of NP solving in Drosophila . We show that Drosophila learn to discriminate a simple component (A or B) associated with electric shocks (+) from an odour mixture composed either partly (called ‘feature-negative discrimination’ A + versus AB − ) or entirely (called ‘NP’ A + B + versus AB − ) of the shock-associated components. Furthermore, we show that conditioning repetition results in a transition from an elemental to a configural representation of the mixture required to solve the NP task, highlighting the cognitive flexibility of Drosophila .

Kir3 channel blockade in the cerebellar cortex suppresses performance of classically conditioned Purkinje cell responses

In the eyeblink conditioning paradigm, cerebellar Purkinje cells learn to respond to the conditional stimulus with an adaptively timed pause in its spontaneous firing. Evidence suggests that the pause is elicited by glutamate released from parallel fibers and acting on metabotropic receptors (mGluR7) which initiates a delayed-onset suppression of firing. We suggested that G protein activation of hyperpolarizing Kir3 channels (or ‘GIRK’, G protein-coupled inwardly-rectifying K+ channels) could be part of such a mechanism. Application of the Kir3 antagonist Tertiapin-LQ locally in the superficial layers of the cerebellar cortex in decerebrate ferrets suppressed normal performance of Purkinje cell pause responses to the conditional stimulus. Importantly, there was no detectable effect on spontaneous firing. These findings suggest that intact functioning of Kir3 channels in the cerebellar cortex is required for normal conditioned Purkinje cell responses.

A Stusy of TMS For Extinction about Early Traumatic Memory Description

Individuals will experience strong traumatic memories after traumatic events such as earthquakes, car accidents, or loss of loved ones, the most common of which is fear memory. In this experiment, a multi-sensory compound stimulation model (electric stimulation + picture) was used as the conditional stimulus, and the skin electrical response was used as the index of fear response. The effect of retrieval-extinction paradigm on the conditional fear extinction was tested. In addition, high-frequency rTMS was introduced as a treatment.To explore the therapeutic effect of TMS on conditional fear, with the aim of providing new measures for the treatment of PTSD.