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Dryden, M.

Publications and source records attributed to Dryden, M..

3 recordsLinked to original sources

Distinct Electrophysiological Signatures Define Neuronal Subtypes in the Fasciola Cinereum

The fasciola cinereum (FC) is a small, conserved hippocampal subregion whose cellular properties remain poorly understood. Anatomically positioned between dorsal CA1 and the third ventricle, the FC receives diverse cortical and subcortical inputs but is often excluded from hippocampal circuit models. Here, we performed ex vivo whole-cell patch-clamp recordings in mouse hippocampal slices to define the intrinsic and synaptic properties of FC neurons. We find that FC neurons are electrophysiologically and morphologically distinct from neighboring CA1 and CA2 pyramidal cells, exhibiting reduced intrinsic excitability, delayed spike initiation, and enhanced afterhyperpolarizations. These properties are strongly shaped by potassium conductances, with Kv2 (KCNB) and Kv7 (KCNQ) channels contributing to the suppression of firing. We find that FC neurons span a continuum of intrinsic excitability which is structured by variability in potassium channel-mediated conductances and is inversely coordinated with excitatory synaptic input, such that less excitable neurons receive stronger synaptic drive. Together, these findings establish a mechanistic framework in which intrinsic membrane properties and synaptic input are co-organized across the FC population, providing new insight into how this understudied hippocampal region may contribute to the regulation of neural excitability. Key PointsO_LIThe fasciola cinereum (FC) is a small and poorly understood hippocampal subregion that has recently been implicated in hippocampal related function and seizure activity. C_LIO_LIHere we show that neurons in the FC are morphologically and functionally distinct from cells in neighboring CA1 and CA2 hippocampal subregions, and find substantial physiological diversity of FC neurons, including differences in firing behavior, membrane properties, and intrinsic excitability. C_LIO_LIPharmacological analyses show that Kv2 and Kv7 potassium channels play a key role in shaping the intrinsic properties of FC neurons. C_LIO_LILess excitable FC neurons receive stronger excitatory synaptic input, revealing an inverse relationship between intrinsic membrane excitability and synaptic drive. C_LIO_LIThese findings identify the FC as a physiologically specialized hippocampal subregion and provide a foundation for understanding its role in hippocampal function and neurological disease. C_LI

neuroscience↗

Pharmacological manipulations of the dorsomedial and dorsolateral striatum during fear extinction have opposing effects on fear renewal

Systemic manipulations that enhance dopamine (DA) transmission around the time of fear extinction can strengthen fear extinction and reduce conditioned fear relapse. Prior studies investigating the brain regions where DA augments fear extinction focus on targets of mesolimbic and mesocortical DA systems originating in the ventral tegmental area, given the role of these DA neurons in prediction error. The dorsal striatum (DS), a primary target of the nigrostriatal DA system originating in the substantia nigra (SN), is implicated in behaviors beyond its canonical role in movement, such as reward and punishment, goal-directed action, and stimulus-response associations, but whether DS DA contributes to fear extinction is unknown. We have observed that chemogenetic stimulation of SN DA neurons during fear extinction prevents the return of fear in contexts different from the extinction context, a form of relapse called renewal. This effect of SN DA stimulation is mimicked by a DA D1 receptor (D1R) agonist injected into the DS, thus implicating DS DA in fear extinction. Different DS subregions subserve unique functions of the DS, but it is unclear where in the DS D1R agonist acts during fear extinction to reduce renewal. Furthermore, although fear extinction increases neural activity in DS subregions, whether neural activity in DS subregions is causally involved in fear extinction is unknown. To explore the role of DS subregions in fear extinction, adult, male Long-Evans rats received microinjections of either the D1R agonist SKF38393 or a cocktail consisting of GABAA/GABAB receptor agonists muscimol/baclofen selectively into either dorsomedial (DMS) or dorsolateral (DLS) DS subregions immediately prior to fear extinction, and extinction retention and renewal were subsequently assessed drug-free. While increasing D1R signaling in the DMS during fear extinction did not impact fear extinction retention or renewal, DMS inactivation reduced later renewal. In contrast, DLS inactivation had no effect on fear extinction retention or renewal but increasing D1R signaling in the DLS during extinction reduced fear renewal. These data suggest that DMS and DLS activity during fear extinction can have opposing effects on later fear renewal, with the DMS promoting renewal and the DLS opposing renewal. Mechanisms through which the DS could influence the contextual gating of fear extinction are discussed. HighlightsO_LIDorsolateral striatum D1 receptor signaling during fear extinction reduces renewal C_LIO_LINeural activity in the dorsomedial striatum during fear extinction permits renewal C_LIO_LIDorsal striatum subregions have opposing roles in contextual gating of fear extinction C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=51 SRC="FIGDIR/small/576042v2_ufig1.gif" ALT="Figure 1"> View larger version (8K): org.highwire.dtl.DTLVardef@6d935org.highwire.dtl.DTLVardef@19e51acorg.highwire.dtl.DTLVardef@103fa30org.highwire.dtl.DTLVardef@1e7017_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Temporary anosmia in mice following nasal lavage with dilute detergent solution

Olfactory sensory deprivation induces anosmia and reduces tyrosine hydroxylase and dopamine levels in the olfactory bulb. The behavioral consequences specific to the loss of olfactory bulb dopamine are difficult to determine because sensory deprivation protocols are either confounded by side effects or leave the animal anosmic. A new method to both induce sensory deprivation and to measure the behavioral and circuit consequences is needed. We developed a novel, recoverable anosmia protocol utilizing nasal lavage with a dilute detergent solution. Detergent treatment did not damage the olfactory epithelium as measured by scanning electron microscopy, alcian blue histology, and acetylated tubulin immunohistochemistry. One treatment induced anosmia that lasted 24-48 hours. Lastly, five days of treatment reduced both olfactory bulb tyrosine hydroxylase and dopamine levels which indicates that anosmia persists between treatments. This is the first report of a sensory deprivation protocol that induces recoverable anosmia and can be paired with biochemical, histological, and behavioral investigations of olfaction.

neuroscience↗