Hippocampal sharp wave ripples underlie stress susceptibility in male mice.

The ventral hippocampus (vHC) is a core brain region for emotional memory. Here, we examined how the vHC regulates stress susceptibility from the level of gene expression to neuronal population dynamics in male mice. Transcriptome analysis of samples from stress-naïve mice revealed that intrinsic calbindin (Calb1) expression in the vHC is associated with susceptibility to social defeat stress. Mice with Calb1 gene knockdown in the vHC exhibited increased stress resilience and failed to show the increase in the poststress ventral hippocampal sharp wave ripple (SWR) rate. Poststress vHC SWRs triggered synchronous reactivation of stress memory-encoding neuronal ensembles and facilitated information transfer to the amygdala. Suppression of poststress vHC SWRs by real-time feedback stimulation or walking prevented social behavior deficits. Taken together, our results demonstrate that internal reactivation of memories of negative stressful episodes supported by ventral hippocampal SWRs serves as a crucial neurophysiological substrate for determining stress susceptibility.

Establishment of an unfed strain of Paramecium bursaria and analysis of associated bacterial communities controlling its proliferation.

The ciliate Paramecium bursaria harbors several hundred symbiotic algae in its cell and is widely used as an experimental model for studying symbiosis between eukaryotic cells. Currently, various types of bacteria and eukaryotic microorganisms are used as food for culturing P. bursaria; thus, the cultivation conditions are not uniform among researchers. To unify cultivation conditions, we established cloned, unfed strains that can be cultured using only sterile medium without exogenous food. The proliferation of these unfed strains was suppressed in the presence of antibiotics, suggesting that bacteria are required for the proliferation of the unfed strains. Indeed, several kinds of bacteria, such as Burkholderiales, Rhizobiales, Rhodospirillales, and Sphingomonadales, which are able to fix atmospheric nitrogen and/or degrade chemical pollutants, were detected in the unfed strains. The genetic background of the individually cloned, unfed strains were the same, but the proliferation curves of the individual P. bursaria strains were very diverse. Therefore, we selected multiple actively and poorly proliferating individual strains and compared the bacterial composition among the individual strains using 16S rDNA sequencing. The results showed that the bacterial composition among actively proliferating P. bursaria strains was highly homologous but different to poorly proliferating strains. Using unfed strains, the cultivation conditions applied in different laboratories can be unified, and symbiosis research on P. bursaria will make great progress.

Weak representation of awake/sleep states by local field potentials in aged mice.

Senescence affects various aspects of sleep, and it remains unclear how sleep-related neuronal network activity is altered by senescence. Here, we recorded local field potential signals from multiple brain regions covering the forebrain in young (10-week-old) and aged (2-year-old) mice. Interregional LFP correlations across these brain regions could not detect pronounced differences between awake and sleep states in both young and aged mice. Multivariate analyses with machine learning algorithms with uniform manifold approximation and projection and robust continuous clustering demonstrated that LFP correlational patterns at multiple frequency bands, ranging from delta to high gamma bands, in aged mice less represented awake/sleep states than those in young mice. By housing aged mice in an enriched environment, the LFP patterns were changed to more precisely represent awake/sleep states. Our results demonstrate senescence-induced changes in neuronal activity at the network level and provide insight into the prevention of pathological symptoms associated with sleep disturbance in senescence.

Multiple states in ongoing neural activity in the rat visual cortex.

The brain continuously produces internal activity in the absence of afferently salient sensory input. Spontaneous neural activity is intrinsically defined by circuit structures and associated with the mode of information processing and behavioral responses. However, the spatiotemporal dynamics of spontaneous activity in the visual cortices of behaving animals remain almost elusive. Using a custom-made electrode array, we recorded 32-site electrocorticograms in the primary and secondary visual cortex of freely behaving rats and determined the propagation patterns of spontaneous neural activity. Nonlinear dimensionality reduction and unsupervised clustering revealed multiple discrete states of the activity patterns. The activity remained stable in one state and suddenly jumped to another state. The diversity and dynamics of the internally switching cortical states would imply flexibility of neural responses to various external inputs.

Collection of biochemical samples with brain-wide electrophysiological recordings from a freely moving rodent.

Bridging accumulating insights from microscopic and macroscopic studies in neuroscience research requires monitoring of neuronal population dynamics and quantifying specific molecules or genes from the brain of identical animals. To this end, by minimizing the size and weight of an electrode array, we developed a method that records local field potential signals of multiple brain regions from one side of the hemisphere in a freely moving rodent. At the same time, extracellular cerebrospinal fluid for biochemical assays or a small part of brain tissue samples for gene expression assays are collected from the other side of the hemisphere. This method allows ongoing stable recordings and sample collections for at least two months. The methodological concept is applicable to a wide range of biological reactions at various spatiotemporal scales, allowing us to integrate an idea of physiolomics into existing omics analyses, leading to a new combination of multi-omics approaches.