anisomycin and ifenprodil

Topics: Amygdala; Animals; Anisomycin; CA1 Region, Hippocampal; Clonidine; Cognition; Cysteine Proteinase Inhibitors; Early Growth Response Protein 1; Excitatory Amino Acid Antagonists; Fear; GABA-A Receptor Agonists; Lactones; Memory; Midline Thalamic Nuclei; Muscimol; Neurons; Piperidines; Prefrontal Cortex; Rats; Receptors, N-Methyl-D-Aspartate

Amygdala lesions impair, but do not prevent, acquisition of cerebellum-dependent eyeblink conditioning suggesting that the amygdala modulates cerebellar learning. Two-factor theories of eyeblink conditioning posit that a fast-developing memory within the amygdala facilitates slower-developing memory within the cerebellum. The current study tested this hypothesis by impairing memory consolidation within the amygdala with inhibition of protein synthesis, transcription, and NMDA receptors in rats. Rats given infusions of anisomycin or DRB into the central amygdala (CeA) immediately after each eyeblink conditioning session were severely impaired in contextual and cued fear conditioning, but were completely unimpaired in eyeblink conditioning. Rats given the NMDA antagonist ifenprodil into the CeA before each eyeblink conditioning session also showed impaired fear conditioning, but no deficit in eyeblink conditioning. The results indicate that memory formation within the CeA is not necessary for its modulation of cerebellar learning mechanisms. The CeA may modulate cerebellar learning and retention through an attentional mechanism that develops within the training sessions.

Topics: Animals; Anisomycin; Central Amygdaloid Nucleus; Cerebellum; Conditioning, Classical; Conditioning, Eyelid; Dichlororibofuranosylbenzimidazole; Electromyography; Excitatory Amino Acid Antagonists; Male; Memory Consolidation; Piperidines; Protein Synthesis Inhibitors; Rats; Rats, Long-Evans

Signaling at NMDA receptors (NMDARs) is known to be important for memory reconsolidation, but while most studies show that NMDAR antagonists prevent memory restabilization and produce amnesia, others have shown that GluN2B-selective NMDAR antagonists prevent memory destabilization, protecting the memory. These apparently paradoxical, conflicting data provide an opportunity to define more precisely the requirement for different NMDAR subtypes in the mechanisms underlying memory reconsolidation and to further understand the contribution of glutamatergic signaling to this process. Here, using rats with fully consolidated pavlovian auditory fear memories, we demonstrate a double dissociation in the requirement for GluN2B-containing and GluN2A-containing NMDARs within the basolateral amygdala in the memory destabilization and restabilization processes, respectively. We further show a double dissociation in the mechanisms underlying memory retrieval and memory destabilization, since AMPAR antagonism prevented memory retrieval while still allowing the destabilization process to occur. These data demonstrate that glutamatergic signaling mechanisms within the basolateral amygdala differentially and dissociably mediate the retrieval, destabilization, and restabilization of previously consolidated fear memories.

Topics: Amygdala; Animals; Anisomycin; Association Learning; Excitatory Amino Acid Antagonists; Fear; Male; Memory; Piperidines; Protein Synthesis Inhibitors; Quinoxalines; Rats; Receptors, N-Methyl-D-Aspartate

Hippocampal long-term depression (LTD) comprises a persistent reduction of synaptic strength that is typically induced by low frequency stimulation (LFS). Although LTD has been described for the dentate gyrus in vitro, this phenomenon in the dentate gyrus of the intact animal is less well understood. In the current study, we investigated the contribution of NMDA receptors, L-type voltage gated calcium channels and protein synthesis to LFS-induced LTD in the dentate gyrus of freely moving rats. Animals were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. LTD persisted for at least 24h, and was unaffected by prior treatment with the NMDA receptor antagonists AP5 or ifenprodil, which, in contrast, prevented LTP. Neither the L-type voltage-gated calcium channel antagonist, methoxyverapamil, nor the protein translation inhibitors, anisomycin or emetine had an effect on the profile of LTD. Our results suggest that NMDA receptors and L-type voltage-gated calcium channels are not involved in the induction of LTD in the dentate gyrus in vivo. Intriguingly, persistent LTD can be established without the synthesis of new proteins, suggesting that in the dentate gyrus, alternative mechanisms exist for the sustainment of enduring LTD.

Topics: 2-Amino-5-phosphonovalerate; Animals; Anisomycin; Calcium Channel Blockers; Calcium Channels, L-Type; Dentate Gyrus; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Electric Stimulation; Emetine; Excitatory Amino Acid Antagonists; Gallopamil; Long-Term Synaptic Depression; Male; Piperidines; Protein Synthesis Inhibitors; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Time Factors; Wakefulness