The timing and specificity of oligodendrocyte myelination during development, as well as remyelination after injury or immune attack, remain poorly understood. Recent work has shown that oligodendrocyte progenitors receive synapses from neurons, providing a potential mechanism for neuronal-glial communication. In this study, we investigated the importance of these neuroglial connections in myelination during development and during neuronal plasticity in the mouse hippocampus. We used chemogenetic tools and viral monosynaptic circuit tracing to analyze these connections and to examine oligodendrocyte progenitor cells (OPCs) proliferation, myelination, synapse formation, and neuronal-glial connectivity in vivo after increasing or decreasing neuronal activity levels . We found that increasing neuronal activity led to greater OPC activation and proliferation. Modulation of neuronal activity also altered the organization of neuronal-glial connections: while it did not impact the total number of RabV-labeled neu...

Respiratory sinus arrhythmia (RSA), the natural variation in heart rate synchronized with respiration, has been extensively studied in emotional and cognitive contexts. Various time or frequency-based methods using the cardiac signal have been proposed to analyze RSA. In this study, we present a novel approach that combines respiratory phase and heart rate to enable a more detailed analysis of RSA and its dynamics throughout the respiratory cycle. To facilitate the application of this method, we have implemented it in an open-source Python toolbox called physio. This toolbox includes essential functionalities for processing electrocardiogram (ECG) and respiratory signals, while also introducing this new approach for RSA analysis. Inspired by previous research conducted by our group, this method enables a cycle-by-cycle analysis of RSA providing the possibility to correlate any respiratory feature to any RSA feature. By employing this approach, we aim to gain a more accurate understanding of the neural mech...

The auditory system relies on both local and summary representations; acoustic local features exceeding system constraints are compacted into a set of summary statistics. Such compression is pivotal for sound-object recognition. Here, we assessed whether computations subtending local and statistical representations of sounds could be distinguished at the neural level. A computational auditory model was employed to extract auditory statistics from natural sound textures (i.e., fire, rain) and to generate synthetic exemplars where local and statistical properties were controlled. Twenty-four human participants were passively exposed to auditory streams while the electroencephalography (EEG) was recorded. Each stream could consist of short, medium, or long sounds to vary the amount of acoustic information. Short and long sounds were expected to engage local or summary statistics representations, respectively. Data revealed a clear dissociation. Compared with summary-based ones, auditory-evoked responses based...

Hippocampal inhibitory neurons (INs) contact local targets and project to different brain areas to form synapses on distal neurons. Despite the importance of INs for hippocampal function and interregional brain communication, the impact of activity-dependent plasticity mechanisms on local and long-range GABAergic synapses formed by hippocampal INs remains to be fully elucidated. Here, we use optogenetic-coupled electrophysiology in mice to show that protein kinase A (PKA), a master regulator of GABAergic synapse plasticity, causes a form of long-term potentiation of inhibitory synapses (iLTP) in hippocampal granule cells (GCs). This form of iLTP is observed in GCs synapses originated in local INs expressing the marker somatostatin (SST), but not in those expressing parvalbumin. Long-range synapses formed by SST INs onto medial septum neurons are unaffected by PKA activation. iLTP of local SST synapses on GCs is accompanied by changes in presynaptic probability of release and is occluded by pharmacological ...

Spoken language contains information at a broad range of timescales, from phonetic distinctions on the order of milliseconds to semantic contexts which shift over seconds to minutes. It is not well understood how the brain’s speech production systems combine features at these timescales into a coherent vocal output. We investigated the spatial and temporal representations in cerebral cortex of three phonological units with different durations: consonants, vowels, and syllables. Electrocorticography (ECoG) recordings were obtained from five participants while speaking single syllables. We developed a novel clustering and Kalman filter-based trend analysis procedure to sort electrodes into temporal response profiles. A linear discriminant classifier was used to determine how strongly each electrode’s response encoded phonological features. We found distinct time-courses of encoding phonological units depending on their duration: consonants were represented more during speech preparation, vowels were represen...

Depression is a frequent and serious illness, and stress is considered the main risk factor for its onset. First-line antidepressants increase serotonin (5-hydroxytryptamine; 5-HT) levels in the brain. We previously reported that an N -acetyltransferase, Shati/Nat8l, is upregulated in the dorsal striatum (dSTR) of stress-susceptible mice exposed to repeated social defeat stress (RSDS) and that dSTR Shati/Nat8l overexpression in mice (dSTR-Shati OE) induces stress vulnerability and local reduction in 5-HT content. Male mice were used in this study, and we found that dSTR 5-HT content decreased in stress-susceptible but not in resilient mice. Moreover, vulnerability to stress in dSTR-Shati OE mice was suppressed by the activation of serotonergic neurons projecting from the dorsal raphe nucleus (dRN) to the dSTR, followed by upregulation of 5-HT content in the dSTR using designer receptors exclusively activated by designer drugs (DREADD). We evaluated the role of GABA in modulating the serotonergic system in ...

Lysosomes are acidic organelles that traffic throughout neurons delivering catabolic enzymes to distal regions of the cell and maintaining degradative demands. Loss of function mutations in the gene GBA encoding the lysosomal enzyme glucocerebrosidase (GCase) cause the lysosomal storage disorder Gaucher’s disease (GD) and are the most common genetic risk factor for synucleinopathies like Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). GCase degrades the membrane lipid glucosylceramide (GlcCer) and mutations in GBA , or inhibiting its activity, results in the accumulation of GlcCer and disturbs the composition of the lysosomal membrane. The lysosomal membrane serves as the platform to which intracellular trafficking complexes are recruited and activated. Here, we investigated whether lysosomal trafficking in axons was altered by inhibition of GCase with the pharmacological agent Conduritol B Epoxide (CBE). Using live cell imaging in human male induced pluripotent human stem cell (iPSC)-derived...

The intercalated cells of the amygdala (ITCs) are a fundamental processing structure in the amygdala that remain relatively understudied. They are phylogenetically conserved from insectivores through primates, inhibitory, and project to several of the main processing and output stations of the amygdala and basal forebrain. Through these connections, the ITCs are best known for their role in conditioned fear, where they are required for fear extinction learning and recall. Prior work on ITC connectivity is limited, and thus holistic characterization of their afferent and efferent connectivity in a genetically defined manner is incomplete. The ITCs express the FoxP2 transcription factor, affording genetic access to these neurons for viral input-output mapping. To fully characterize the anatomic connectivity of the ITCs, we used cre-dependent viral strategies in FoxP2-cre mice to reveal the projections of the main (mITC), caudal (cITC), and lateral (lITC) clusters along with their presynaptic sources of inner...

Motor learning and flexibility allow animals to perform routine actions efficiently while keeping them flexible. A number of paradigms are used to test cognitive flexibility, but not many of them focus specifically on the learning of complex motor sequences and their flexibility. While many tests use operant or touchscreen boxes that offer high throughput and reproducibility, the motor actions themselves are mostly simple presses of a designated lever. To focus more on motor actions during the operant task and to probe the flexibility of these well trained actions, we developed a new operant paradigm for mice, the “timed sequence task.” The task requires mice to learn a sequence of lever presses that have to be emitted in precisely defined time limits. After training, the required pressing sequence and/or timing of individual presses is modified to test the ability of mice to alter their previously trained motor actions. We provide a code for the new protocol that can be used and adapted to common types of...

The retinas of the vast majority of vertebrate species are termed “duplex,” that is, they contain both rod and cone photoreceptor neurons in different ratios. The retina of little skate ( Leucoraja erinacea ) is a rarity among vertebrates because it contains only a single photoreceptor cell type and is thus “simplex.” This unique retina provides us with an important comparative model and an exciting opportunity to study retinal circuitry within the context of a visual system with a single photoreceptor cell type. What is perhaps even more intriguing is the fact that the Leucoraja retina is able use that single photoreceptor cell type to function under both scotopic and photopic ranges of illumination. Although some ultrastructural characteristics of skate photoreceptors have been examined previously, leading to a general description of them as “rods” largely based on outer segment (OS) morphology and rhodopsin expression, a detailed study of the fine anatomy of the entire cell and its synaptic connectivity...