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 utilized chemogenetic tools and viral monosynaptic circuit tracing to analyze these connections and to examine oligodendrocyte progenitor cells (OPC) 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 n...

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 and 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 i...

During free viewing, we move our eyes and fixate on objects to recognize the visual scene of our surroundings. To investigate the neural representation of objects in this process, we studied individual and population neuronal activity in three different visual regions of the brains of macaque monkeys ( Macaca fuscata ): the primary and secondary visual cortices and the inferotemporal cortex. We designed a task where the animal freely selected objects in a stimulus image to fixate on while we examined the relationship between spiking activity, the order of fixations, and the fixated objects. We found that activity changed across repeated fixations on the same object in all three recorded areas, with observed reductions in firing rates. Furthermore, the responses of individual neurons became sparser and more selective with individual objects. The population activity for individual objects also became distinct. These results suggest that visual neurons respond dynamically to repeated input stimuli through a s...

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 ...

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...

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...

The Drosophila mushroom body (MB) is an important model system for studying the synaptic mechanisms of associative learning. In this system, coincidence of odor-evoked calcium influx and dopaminergic input in the presynaptic terminals of Kenyon cells (KCs), the principal neurons of the MB, triggers long-term depression (LTD), which plays a critical role in olfactory learning. However, it is controversial whether such synaptic plasticity is accompanied by a corresponding decrease in odor-evoked calcium activity in the KC presynaptic terminals. Here, we address this question by inducing LTD by pairing odor presentation with optogenetic activation of dopaminergic neurons (DANs). This allows us to rigorously compare the changes at the presynaptic and postsynaptic sites in the same conditions. By imaging presynaptic acetylcholine release in the condition where LTD is reliably observed in the postsynaptic calcium signals, we show that neurotransmitter release from KCs is depressed selectively in the MB compartme...

Traumatic brain injury (TBI) affects millions of people annually and is a leading cause of long-term disability. Individuals with this condition commonly manifest behavioral, psychiatric, and cognitive dysfunctions, yet there is inadequate understanding of underlying mechanisms, posing challenges for effective treatments. TBI often arises from physical trauma to the head resulting in focal or diffuse injury, long-term cell loss, and tissue damage depending on injury type. Focal injuries can be modeled with the controlled cortical impact (CCI), while fluid percussion injury (FPI) models diffuse concussive injuries. Furthermore, each type of injury can be further classified based on severity (e.g., mild, moderate, and severe), each with their own unique pathophysiology. In mild TBI, diffuse injury leads to cell loss, diffuse axonal injury, and related circuit alterations in both afferent and efferent networks connecting to the injured cortical area (Krishna et al., 2020). It is recognized that dysfunction of...

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 ...

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...