The role of sleep in emotional processing: insights and unknowns from rodent research

International audienceSleep is essential for the regulation of neural dynamics and animal behavior. In particular, sleep is crucial for memory consolidation and emotional regulation. In turn, emotions are key to the modulation of learning processes in which sleep also plays a crucial role. Emotional processing triggers coordinated activity between neuronal populations embedded in a network including the hippocampus, amygdala and prefrontal cortex. The optogenetic modulation of these distributed engrams' activity interferes with emotional memory. During non-REM sleep, cross-structure coordinated replay may underpin the consolidation of brain-wide emotional associative engrams. Fear conditioning induces neural synchronization between the amygdala, hippocampus, and medial prefrontal cortex during subsequent REM sleep, the perturbation of which interferes with fear memory consolidation. Future work may focus on the differential mechanisms during REM vs non-REM sleep that underpin emotional regulation and memory consolidation, as well as on distinguishing between these two tightly linked cognitive processes

Functional characterization of the basal amygdala - dorsal BNST pathway during contextual fear conditioning

International audienceBoth the basal amygdala (BA) and the bed nucleus of the stria terminalis (BNST) can participate in contextual fear, but it is unclear if contextual fear engrams involve a direct interaction between these two brain regions. To determine if dorsal BNST (dBNST)-projecting neurons in the BA participate in contextual fear engrams, we combined the TetTag mouse with a retrograde tracer to label dBNST-projecting cells in the BA. We identified a population of neurons located in the anterior subdivision of the BA that was activated during fear conditioning and reactivated during retrieval, but that did not project to the dBNST. In contrast, dBNST-projecting neurons located in the posterior BA were activated during contextual fear conditioning, but were not reactivated during retrieval. Similarly, we found neurons in the oval BNST subdivision (ovBNST) that were activated during contextual fear conditioning without being reactivated during retrieval. However, the anterodorsal BNST subdivision (adBNST) was not activated during either contextual fear conditioning or retrieval, underscoring the divergent functionality of these two dBNST subdivisions. Finally, we found that the ovBNST receives a monosynaptic projection from neurons located in the BA. Our results indicate that anterior BA neurons that do not project to the dBNST participate in contextual fear engrams. In contrast, dBNST-projecting neurons in the BA do not appear to participate in contextual fear engrams, but might instead contain a BA → ovBNST pathway that is active during the initial encoding of contextual fear memories.SIGNIFICANCE STATEMENT Both the basal amygdala (BA) and the dorsal bed nucleus of the stria terminalis (dBNST) can participate in contextual fear, but it is unclear if this reflects a direct interaction between these two brain regions. BA neurons that do not project to the dBNST were found to be active during both the encoding and retrieval of a contextual fear memory, indicating their participation in a contextual fear engram. In contrast, BA neurons that do project to the dBNST were found to be active during the encoding, but not the retrieval of a contextual fear memory. These findings suggest a direct interaction between the BA and dBNST during the initial encoding, but not the subsequent storage of contextual fear memories

Amyloid beta immunization worsens iron deposits in the choroid plexus and cerebral microbleeds

International audienceAnti-amyloid beta (Aβ) immunotherapy provides potential benefits in Alzheimer's disease patients. Nevertheless, strategies based on Aβ1-42 peptide induced encephalomyelitis and possible microhemorrhages. These outcomes were not expected from studies performed in rodents. It is critical to determine if other animal models better predict side effects of immunotherapies. Mouse lemur primates can develop amyloidosis with aging. Here we used old lemurs to study immunotherapy based on Aβ1-42 or Aβ-derivative (K6Aβ1-30). We followed anti-Aβ40 immunoglobulin G and M responses and Aβ levels in plasma. In vivo magnetic resonance imaging and histology were used to evaluate amyloidosis, neuroinflammation, vasogenic edema, microhemorrhages, and brain iron deposits. The animals responded mainly to the Aβ1-42 immunogen. This treatment induced immune response and increased Aβ levels in plasma and also microhemorrhages and iron deposits in the choroid plexus. A complementary study of untreated lemurs showed iron accumulation in the choroid plexus with normal aging. Worsening of iron accumulation is thus a potential side effect of Aβ-immunization at prodromal stages of Alzheimer's disease, and should be monitored in clinical trials