Browsing by keyword "Avoidance Learning"
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Different kenyon cell populations drive learned approach and avoidance in DrosophilaIn Drosophila, anatomically discrete dopamine neurons that innervate distinct zones of the mushroom body (MB) assign opposing valence to odors during olfactory learning. Subsets of MB neurons have temporally unique roles in memory processing, but valence-related organization has not been demonstrated. We functionally subdivided the alphabeta neurons, revealing a value-specific role for the approximately 160 alphabeta core (alphabetac) neurons. Blocking neurotransmission from alphabeta surface (alphabetas) neurons revealed a requirement during retrieval of aversive and appetitive memory, whereas blocking alphabetac only impaired appetitive memory. The alphabetac were also required to express memory in a differential aversive paradigm demonstrating a role in relative valuation and approach behavior. Strikingly, both reinforcing dopamine neurons and efferent pathways differentially innervate alphabetac and alphabetas in the MB lobes. We propose that conditioned approach requires pooling synaptic outputs from across the alphabeta ensemble but only from the alphabetas for conditioned aversion.
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Dopamine reveals neural circuit mechanisms of fly memoryA goal of memory research is to understand how changing the weight of specific synapses in neural circuits in the brain leads to an appropriate learned behavioral response. Finding the relevant synapses should allow investigators to probe the underlying physiological and molecular operations that encode memories and permit their retrieval. In this review I discuss recent work in Drosophila that implicates specific subsets of dopaminergic (DA) neurons in aversive reinforcement and appetitive motivation. The zonal architecture of these DA neurons is likely to reveal the functional organization of aversive and appetitive memory in the mushroom bodies. Combinations of fly DA neurons might code negative and positive value, consistent with a motivational systems role as proposed in mammals.
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Evolutionary conserved role for TARPs in the gating of glutamate receptors and tuning of synaptic functionNeurotransmission in the brain is critically dependent on excitatory synaptic signaling mediated by AMPA-class ionotropic glutamate receptors (AMPARs). AMPARs are known to be associated with Transmembrane AMPA receptor Regulatory Proteins (TARPs). In vertebrates, at least four TARPs appear to have redundant roles as obligate chaperones for AMPARs, thus greatly complicating analysis of TARP participation in synaptic function. We have overcome this limitation by identifying and mutating the essential set of TARPs in C. elegans (STG-1 and STG-2). In TARP mutants, AMPAR-mediated currents and worm behaviors are selectively disrupted despite apparently normal surface expression and clustering of the receptors. Reconstitution experiments indicate that both STG-1 and STG-2 can functionally substitute for vertebrate TARPs to modify receptor function. Thus, we show that TARPs are obligate auxiliary subunits for AMPARs with a primary, evolutionarily conserved functional role in the modification of current kinetics.
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Hippocampal c-Jun-N-terminal kinases serve as negative regulators of associative learningIn the adult mouse, signaling through c-Jun N-terminal kinases (JNKs) links exposure to acute stress to various physiological responses. Inflammatory cytokines, brain injury and ischemic insult, or exposure to psychological acute stressors induce activation of hippocampal JNKs. Here we report that exposure to acute stress caused activation of JNKs in the hippocampal CA1 and CA3 subfields, and impaired contextual fear conditioning. Conversely, intrahippocampal injection of JNKs inhibitors sp600125 (30 mum) or D-JNKI1 (8 mum) reduced activity of hippocampal JNKs and rescued stress-induced deficits in contextual fear. In addition, intrahippocampal administration of anisomycin (100 mug/mul), a potent JNKs activator, mimicked memory-impairing effects of stress on contextual fear. This anisomycin-induced amnesia was abolished after cotreatment with JNKs selective inhibitor sp600125 without affecting anisomycin's ability to effectively inhibit protein synthesis as measured by c-Fos immunoreactivity. We also demonstrated milder and transient activation of the JNKs pathway in the CA1 subfield of the hippocampus during contextual fear conditioning and an enhancement of contextual fear after pharmacological inhibition of JNKs under baseline conditions. Finally, using combined biochemical and transgenic approaches with mutant mice lacking different members of the JNK family (Jnk1, Jnk2, and Jnk3), we provided evidence that JNK2 and JNK3 are critically involved in stress-induced deficit of contextual fear, while JNK1 mainly regulates baseline learning in this behavioral task. Together, these results support the possibility that hippocampal JNKs serve as a critical molecular regulator in the formation of contextual fear.
