Persistent Interruption in Parvalbumin-Positive Inhibitory Interneurons: Biophysical and Mathematical Mechanisms.

Persistent activity in excitatory pyramidal cells (PYRs) is a putative mechanism for maintaining memory traces during working memory. We have recently demonstrated persistent interruption of firing in fast-spiking parvalbumin-expressing interneurons (PV-INs), a phenomenon that could serve as a substrate for persistent activity in PYRs through disinhibition lasting hundreds of milliseconds. Here, we find that hippocampal CA1 PV-INs exhibit type 2 excitability, like striatal and neocortical PV-INs.

Functional specialization of hippocampal somatostatin-expressing interneurons.

Hippocampal somatostatin-expressing () GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single-cell transcriptome analyses have provided a comprehensive -IN subpopulations census, a plausible molecular ground truth of neuronal identity whose links to specific functionality remain incomplete. Here, we designed an approach to identify and access subpopulations of -INs based on transcriptomic features.

Persistent Interruption in Parvalbumin Positive Inhibitory Interneurons: Biophysical and Mathematical Mechanisms.

Persistent activity in principal cells is a putative mechanism for maintaining memory traces during working memory. We recently demonstrated persistent interruption of firing in fast-spiking parvalbumin-expressing interneurons (PV-INs), a phenomenon which could serve as a substrate for persistent activity in principal cells through disinhibition lasting hundreds of milliseconds. Here, we find that hippocampal CA1 PV-INs exhibit type 2 excitability, like striatal and neocortical PV-INs.

Functional specialization of hippocampal somatostatin-expressing interneurons.

Hippocampal somatostatin-expressing () GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single cell transcriptome analyses have provided a comprehensive -IN subtype census, a plausible molecular ground truth of neuronal identity whose links to specific functionality remain incomplete. Here, we designed an approach to identify and access subpopulations of -INs based on transcriptomic features.

Brief synaptic inhibition persistently interrupts firing of fast-spiking interneurons.

Neurons perform input-output operations that integrate synaptic inputs with intrinsic electrical properties; these operations are generally constrained by the brevity of synaptic events. Here, we report that sustained firing of CA1 hippocampal fast-spiking parvalbumin-expressing interneurons (PV-INs) can be persistently interrupted for several hundred milliseconds following brief GABAR-mediated inhibition in vitro and in vivo. A single presynaptic neuron could interrupt PV-IN firing, occasionally with a single action potential (AP), and reliably with AP bursts.

Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity.

Cannabidiol (CBD), a non-euphoric component of cannabis, reduces seizures in multiple forms of pediatric epilepsies, but the mechanism(s) of anti-seizure action remain unclear. In one leading model, CBD acts at glutamatergic axon terminals, blocking the pro-excitatory actions of an endogenous membrane phospholipid, lysophosphatidylinositol (LPI), at the G-protein-coupled receptor GPR55. However, the impact of LPI-GPR55 signaling at inhibitory synapses and in epileptogenesis remains underexplored.

Fxr1 regulates sleep and synaptic homeostasis.

The fragile X autosomal homolog 1 (Fxr1) is regulated by lithium and has been GWAS-associated with schizophrenia and insomnia. Homeostatic regulation of synaptic strength is essential for the maintenance of brain functions and involves both cell-autonomous and system-level processes such as sleep. We examined the contribution of Fxr1 to cell-autonomous homeostatic synaptic scaling and neuronal responses to sleep loss, using a combination of gene overexpression and Crispr/Cas9-mediated somatic knockouts to modulate gene expression.

Slow-decaying presynaptic calcium dynamics gate long-lasting asynchronous release at the hippocampal mossy fiber to CA3 pyramidal cell synapse.

Action potentials trigger two modes of neurotransmitter release, with a fast synchronous component and a temporally delayed asynchronous release. Asynchronous release contributes to information transfer at synapses, including at the hippocampal mossy fiber (MF) to CA3 pyramidal cell synapse where it controls the timing of postsynaptic CA3 pyramidal neuron firing. Here, we identified and characterized the main determinants of asynchronous release at the MF-CA3 synapse.

Synaptic Mechanisms Underlying the Network State-Dependent Recruitment of VIP-Expressing Interneurons in the CA1 Hippocampus.

Disinhibition is a widespread circuit mechanism for information selection and transfer. In the hippocampus, disinhibition of principal cells is provided by the interneuron-specific interneurons that express the vasoactive intestinal polypeptide (VIP-IS) and innervate selectively inhibitory interneurons. By combining optophysiological experiments with computational models, we determined the impact of synaptic inputs onto the network state-dependent recruitment of VIP-IS cells.

Ultrafast Two-Photon Imaging of a High-Gain Voltage Indicator in Awake Behaving Mice.

Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity.

Distinct dampening effects of progesterone on the activity of nucleus tractus solitarii neurons in rat pups.

New Findings: What is the central question of the study? Progesterone is considered a respiratory stimulant drug, but its effect on medullary respiratory neurons are poorly documented. We investigated whether progesterone alters spontaneous activity of neurons in the nucleus of the solitary tract (NTS). What is the main finding and its importance? In NTS neurons, progesterone decreases the action potential firing frequency in response to current injections and the amplitude of excitatory postsynaptic currents.

Respiratory motoneuron properties during the transition from gill to lung breathing in the American bullfrog.

Amphibian respiratory development involves a dramatic metamorphic transition from gill to lung breathing and coordination of distinct motor outputs. To determine whether the emergence of adult respiratory motor patterns was associated with similarly dramatic changes in motoneuron (MN) properties, we characterized the intrinsic electrical properties of American bullfrog trigeminal MNs innervating respiratory muscles comprising the buccal pump. In premetamorphic tadpoles (TK stages IX-XVIII) and adult frogs, morphometric analyses and whole cell recordings were performed in trigeminal MNs identified by fluorescent retrograde labeling.

Calcium extrusion mechanisms in dendrites of mouse hippocampal CA1 inhibitory interneurons.

Local circuit GABAergic inhibitory interneurons control the integration and transfer of information in many brain regions. Several different forms of plasticity reported at interneuron excitatory synapses are triggered by cell- and synapse-specific postsynaptic calcium (Ca) mechanisms. To support this function, the spatiotemporal dynamics of dendritic Ca elevations must be tightly regulated.

Connectivity and network state-dependent recruitment of long-range VIP-GABAergic neurons in the mouse hippocampus.

GABAergic interneurons in the hippocampus provide for local and long-distance coordination of neurons in functionally connected areas. Vasoactive intestinal peptide-expressing (VIP+) interneurons occupy a distinct niche in circuitry as many of them specialize in innervating GABAergic cells, thus providing network disinhibition. In the CA1 hippocampus, VIP+ interneuron-selective cells target local interneurons.

Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus.

Neuronal communication relies on action potential discharge, with the frequency and the temporal precision of action potentials encoding information. Hippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation of glutamate release displayed during granule cell burst firing. However, the spiking patterns required to trigger action potential firing in CA3 pyramidal neurons remain poorly understood.

Mental Illnesses-Associated Fxr1 and Its Negative Regulator Gsk3β Are Modulators of Anxiety and Glutamatergic Neurotransmission.

Genetic variants of the fragile X mental retardation syndrome-related protein 1 ( have been associated to mood regulation, schizophrenia, and bipolar disorders. Nonetheless, genetic association does not indicate a functional link of a given gene to neuronal activity and associated behaviors. In addition, interaction between multiple genes is often needed to sculpt complex traits such as behavior.

Sex-Specific Consequences of Neonatal Stress on Cardio-Respiratory Inhibition Following Laryngeal Stimulation in Rat Pups.

The presence of liquid near the larynx of immature mammals triggers prolonged apneas with significant O desaturations and bradycardias. When excessive, this reflex (the laryngeal chemoreflex; LCR) can be fatal. Our understanding of the origins of abnormal LCR are limited; however, perinatal stress and male sex are risk factors for cardio-respiratory failure in infants.

Fast two-photon imaging of subcellular voltage dynamics in neuronal tissue with genetically encoded indicators.

Monitoring voltage dynamics in defined neurons deep in the brain is critical for unraveling the function of neuronal circuits but is challenging due to the limited performance of existing tools. In particular, while genetically encoded voltage indicators have shown promise for optical detection of voltage transients, many indicators exhibit low sensitivity when imaged under two-photon illumination. Previous studies thus fell short of visualizing voltage dynamics in individual neurons in single trials.

Short-Term Facilitation at a Detonator Synapse Requires the Distinct Contribution of Multiple Types of Voltage-Gated Calcium Channels.

Neuronal calcium elevations are shaped by several key parameters, including the properties, density, and the spatial location of voltage-gated calcium channels (VGCCs). These features allow presynaptic terminals to translate complex firing frequencies and tune the amount of neurotransmitter released. Although synchronous neurotransmitter release relies on both P/Q- and N-type VGCCs at hippocampal mossy fiber-CA3 synapses, the specific contribution of VGCCs to calcium dynamics, neurotransmitter release, and short-term facilitation remains unknown.

Functionally heterogeneous synaptic vesicle pools support diverse synaptic signalling.

Synaptic communication between neurons is a highly dynamic process involving specialized structures. At the level of the presynaptic terminal, neurotransmission is ensured by fusion of vesicles to the membrane, which releases neurotransmitter in the synaptic cleft. Depending on the level of activity experienced by the terminal, the spatiotemporal properties of calcium invasion will dictate the timing and the number of vesicles that need to be released.

Vesicles derived via AP-3-dependent recycling contribute to asynchronous release and influence information transfer.

Action potentials trigger synchronous and asynchronous neurotransmitter release. Temporal properties of both types of release could be altered in an activity-dependent manner. While the effects of activity-dependent changes in synchronous release on postsynaptic signal integration have been studied, the contribution of asynchronous release to information transfer during natural stimulus patterns is unknown.

Interplay between synchronization of multivesicular release and recruitment of additional release sites support short-term facilitation at hippocampal mossy fiber to CA3 pyramidal cells synapses.

Synaptic short-term plasticity is a key regulator of neuronal communication and is controlled via various mechanisms. A well established property of mossy fiber to CA3 pyramidal cell synapses is the extensive short-term facilitation during high-frequency bursts. We investigated the mechanisms governing facilitation using a combination of whole-cell electrophysiological recordings, electrical minimal stimulation, and random-access two-photon microscopy in acute mouse hippocampal slices.

Dendritic inhibition provided by interneuron-specific cells controls the firing rate and timing of the hippocampal feedback inhibitory circuitry.

In cortical networks, different types of inhibitory interneurons control the activity of glutamatergic principal cells and GABAergic interneurons. Principal neurons represent the major postsynaptic target of most interneurons; however, a population of interneurons that is dedicated to the selective innervation of GABAergic cells exists in the CA1 area of the hippocampus. The physiological properties of these cells and their functional relevance for network computations remain unknown.

Inhibitory control of hippocampal inhibitory neurons.

Information processing within neuronal networks is determined by a dynamic partnership between principal neurons and local circuit inhibitory interneurons. The population of GABAergic interneurons is extremely heterogeneous and comprises, in many brain regions, cells with divergent morphological and physiological properties, distinct molecular expression profiles, and highly specialized functions. GABAergic interneurons have been studied extensively during the past two decades, especially in the hippocampus, which is a relatively simple cortical structure.