Kenneth N Fish's research while affiliated with University of Pittsburgh and other places
What is this page?
This page lists the scientific contributions of an author, who either does not have a ResearchGate profile, or has not yet added these contributions to their profile.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
It was automatically created by ResearchGate to create a record of this author's body of work. We create such pages to advance our goal of creating and maintaining the most comprehensive scientific repository possible. In doing so, we process publicly available (personal) data relating to the author as a member of the scientific community.
If you're a ResearchGate member, you can follow this page to keep up with this author's work.
If you are this author, and you don't want us to display this page anymore, please let us know.
Publications (128)
In schizophrenia, layer 3 pyramidal neurons (L3PNs) in the dorsolateral prefrontal cortex (DLPFC) are thought to receive fewer excitatory synaptic inputs and to have lower expression levels of activity-dependent genes and of genes involved in mitochondrial energy production. In concert, these findings from previous studies suggest that DLPFC L3PNs...
Age-related dopamine (DA) neuron loss is a primary feature of Parkinsons disease. However, it remains unclear whether similar biological processes occur during healthy aging, albeit to a lesser degree. We therefore determined whether midbrain DA neurons degenerate during aging in mice and humans. In mice, we identified no changes in midbrain neuron...
Deficient gamma oscillations in prefrontal cortex (PFC) of individuals with schizophrenia appear to involve impaired inhibitory drive from parvalbumin-expressing interneurons (PVIs). Inhibitory drive from PVIs is regulated, in part, by RNA binding fox-1 homolog 1 (Rbfox1). Rbfox1 is spliced into nuclear or cytoplasmic isoforms, which regulate alter...
Background
Dorsolateral prefrontal cortex (DLPFC) dysfunction in schizophrenia appears to reflect alterations in layer 3 pyramidal neurons (L3PNs), including smaller cell bodies and lower expression of mitochondrial energy production genes. However, prior somal size studies used biased strategies for identifying L3PNs, and somal size and levels of...
Parkinson's disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and Drosophila ortholog dVGLUT have been implicated as modulators of DA neuron resilience.However, the mechanisms by which VGLUT2/dV...
Importance:
Individuals with schizophrenia (SZ) exhibit pronounced deficits in somatostatin (SST) messenger RNA (mRNA) levels in the dorsolateral prefrontal cortex (DLPFC). Molecularly distinct subtypes of SST neurons, located in the superficial and deep zones of the DLPFC, are thought to contribute to different functional processes of this region...
Background:
Individuals with schizophrenia are at elevated genetic risks for comorbid cannabis use, and often experience exacerbations of cognitive and psychotic symptoms when exposed to cannabis. These findings have led a number of investigators to examine cannabinoid CB1 receptor (CB1R) alterations in schizophrenia, though with conflicting resul...
Human genetics strongly support the involvement of synaptopathy in psychiatric disorders. However, trans-scale causality linking synapse pathology to behavioral changes is lacking. To address this question, we examined the effects of synaptic inputs on dendrites, cells, and behaviors of mice with knockdown of SETD1A and DISC1, which are validated a...
Background:
Altered glutamatergic neurotransmission may contribute to impaired default mode network (DMN) function in Alzheimer's disease (AD). Among the DMN hub regions, frontal cortex (FC) was suggested to undergo a glutamatergic plasticity response in prodromal AD, while the status of glutamatergic synapses in the precuneus (PreC) during clinic...
Deficient gamma oscillations in prefrontal cortex (PFC) of individuals with schizophrenia appear to involve impaired inhibitory drive from parvalbumin-expressing interneurons (PVIs). Inhibitory drive from PVIs is regulated, in part, by RNA binding fox-1 homolog 1 (Rbfox1). Rbfox1 is spliced into nuclear or cytoplasmic isoforms, which regulate alter...
Objective:
In schizophrenia, somatostatin (SST) and parvalbumin (PV) mRNA levels are lower in the dorsolateral prefrontal cortex (DLPFC), but it remains unclear whether these findings reflect lower transcript levels per neuron, fewer neurons, or both. Distinguishing among these alternatives has implications for understanding the pathogenesis of, a...
Background: Individuals with schizophrenia are at elevated genetic risks for comorbid cannabis use, and often experience exacerbations of cognitive and psychotic symptoms when exposed to cannabis. These findings have led a number of investigators to examine cannabinoid CB1 receptor (CB1R) alterations in schizophrenia, though with conflicting result...
Background
Cognitive deficits in schizophrenia are associated with altered GABA neurotransmission in the prefrontal cortex (PFC). GABA neurotransmission requires GABA synthesis by two isoforms of glutamic acid decarboxylase (GAD65 and GAD67) and packaging by the vesicular GABA transporter (vGAT). Current postmortem findings suggest that GAD67 mRNA...
Neuronal activity evokes a vascular response that is essential to sustain brain function. We show that neurovascular coupling (NVC) is mediated by long-range projecting GABAergic neurons that express Tacr1. Whisker stimulation elicited Tacr1 neuron activity in the barrel cortex through feed-forward excitatory pathways. Optogenetic activation of Tac...
Developing novel treatments for alcohol use disorders (AUDs) is of paramount importance for improving patient outcomes and alleviating the suffering related to the disease. A better understanding of the molecular and neurocircuit mechanisms through which alcohol alters brain function will be instrumental in the rational development of new efficacio...
Total internal reflection fluorescence (TIRF) microscopy (TIRFM) is an elegant optical technique that provides for the excitation of fluorophores in an extremely thin axial region ("optical section"). The method is based on the principle that when excitation light is completely internally reflected in a transparent solid (e.g., coverglass) at its i...
Alterations in cannabinoid CB1 receptor (CB1R) are implicated in various psychiatric disorders. CB1R participates in both depolarization induced suppression of inhibition (DSI) and depolarization induced suppression of excitation (DSE), suggesting its involvement in regulating excitatory and inhibitory (E/I) balance. Prior studies examining neurona...
Recent discoveries of extreme cellular diversity in the brain warrant rapid development of technologies to access specific cell populations within heterogeneous tissue. Available approaches for engineering-targeted technologies for new neuron subtypes are low yield, involving intensive transgenic strain or virus screening. Here, we present Specific...
Alterations in cannabinoid CB1 receptor (CB1R) are implicated in various psychiatric disorders. CB1R participates in both depolarization induced suppression of inhibition (DSI) and depolarization induced suppression of excitation (DSE), suggesting its involvement in regulating excitatory and inhibitory (E/I) balance. Prior studies examining neurona...
Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and the principal interface between dopamine reward signals and functionally diverse cortico-basal ganglia circuits. Information processing in these circuits is dependent on distinct MSN types: cell types that are traditionally defined according to their projection targets...
Age is the greatest risk factor for Parkinson's disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater risk than females. Intriguingly, some DA neurons are more resilient to degeneration than others. Increasing evidence suggests that vesicular glutamate transporter (VGLUT) expression in DA neurons plays a role in...
Parkinson’s disease (PD) is characterized by progressive dopamine (DA) neuron loss in the SNc. In contrast, DA neurons in the VTA are relatively protected from neurodegeneration, but the underlying mechanisms for this resilience remain poorly understood. Recent work suggests that expression of the vesicular glutamate transporter 2 (VGLUT2) selectiv...
Background
Visuospatial working memory (vsWM), which is commonly impaired in schizophrenia, involves information processing across primary visual (V1), association visual (V2), posterior parietal (PPC), and dorsolateral prefrontal (DLPFC) cortices. Within these regions, vsWM requires inhibition from parvalbumin (PV)-expressing basket cells (PVBCs)....
Activation of specific neural circuits in different layers of the primate dorsolateral prefrontal cortex (DLPFC) is essential for working memory, a core cognitive function. Recurrent excitation between pyramidal neurons in middle and deep layers of the DLPFC contributes to the laminar-specific activity associated with different working memory subpr...
The functional output of a cortical region is shaped by its complement of GABA neuron subtypes. GABA-related transcript expression differs substantially between the primate dorsolateral prefrontal cortex (DLPFC) and primary visual (V1) cortices in gray matter homogenates, but the laminar and cellular bases for these differences are unknown. Quantif...
Age is the greatest risk factor for Parkinson’s disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater risk than females. We found that vesicular glutamate transporter (VGLUT) expression mediates vulnerability to age-related DA neurodegeneration in a sex-dependent manner, providing a new mechanism for sex differe...
The striatum is the neural interface between dopamine reward signals and cortico-basal ganglia circuits responsible for value assignments, decisions, and actions. Medium spiny neurons (MSNs) make up the vast majority of striatal neurons and are traditionally classified as two distinct types: direct- and indirect-pathway MSNs. The direct- and indire...
The endoplasmic reticulum (ER) is a highly dynamic network of membranes. Here, we combine live-cell microscopy with in situ cryo–electron tomography to directly visualize ER dynamics in several secretory cell types including pancreatic β-cells and neurons under near-native conditions. Using these imaging approaches, we identify a novel, mobile form...
Several postmortem studies have reported lower levels of immunoreactivity (IR) for microtubule-associated protein 2 (MAP2) in several cortical regions of individuals with schizophrenia (SZ). However, whether this effect is conserved across multiple brain areas within an individual with SZ or if it is regionally-specific remains unclear. We characte...
In primates, working memory function depends on activity in a distributed network of cortical areas that display different patterns of
delay task-related activity. These differences are correlated with, and might depend on, distinctive properties of the neurons located in
each area. For example, layer 3 pyramidal neurons (L3PNs) differ significantl...
In primates, working memory function depends on activity in a distributed network of cortical areas that display different patterns of delay task-related activity. These differences are correlated with, and might depend on, distinctive properties of the neurons located in each area. For example, layer 3 pyramidal neurons (L3PNs) differ significantl...
Previously, we demonstrated that dendritic spine density (DSD) in deep layer 3 of the primary auditory cortex (A1) lower, due to having fewer small spines, in subjects with schizophrenia (SZ) than non-psychiatric control (NPC) subjects. We also previously demonstrated that microtubule-associated-protein-2 immunoreactivity (MAP2-IR) in A1 deep layer...
INTRODUCTION
Our understanding of the pathophysiology of psychiatric disorders, including autism spectrum disorder (ASD), schizophrenia (SCZ), and bipolar disorder (BD), lags behind other fields of medicine. The diagnosis and study of these disorders currently depend on behavioral, symptomatic characterization. Defining genetic contributions to dis...
In human prefrontal cortex (PFC), ~85% of γ-aminobutyric acid (GABA)-expressing neurons can be subdivided into non-overlapping groups by the presence of calbindin (CB), calretinin (CR) or parvalbumin (PV). Substantial research has focused on the differences in the laminar locations of the cells bodies of these neurons, with limited attention to the...
Objective:
Decreased density of dendritic spines in adult schizophrenia subjects has been hypothesized to result from increased pruning of excess synapses in adolescence. In vivo imaging studies have confirmed that synaptic pruning is largely driven by the loss of large or mature synapses. Thus, increased pruning throughout adolescence would likel...
Precuneus (PreC) cortex is affected with amyloid plaques early in Alzheimer's disease (AD), and this pathology may be associated with alterations in PreC synapses and cognitive impairment. We quantified the spinophilin-immunoreactive (ir) dendritic spine density and the intensity of spinophilin immunofluorescence, the latter as a measure of relativ...
Significance
Synaptic pruning in primate prefrontal cortical circuitry has been proposed to contribute to working memory maturation. However, pruning of excitatory synapses has only been shown on pyramidal neurons despite the well-recognized role of parvalbumin (PV) interneurons in working memory. Moreover, in schizophrenia, working memory deficits...
Background:
The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by...
Objective:
Deficient excitatory drive to parvalbumin-containing cortical interneurons is proposed as a key neural substrate for altered gamma oscillations and cognitive dysfunction in schizophrenia. However, a pathological entity producing such a deficit has not been identified. The authors tested the hypothesis that cortical parvalbumin interneur...
Alterations in cortical parvalbumin (PV)-containing neurons, including a reduced density of detectable neurons and lower PV levels, have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. Most PV neurons are surrounded by perineuronal nets (PNNs) and the density of PNNs, as detected by Wisteria floribu...
N-methyl-d-aspartate receptor (NMDAR) hypofunction in the dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathology of schizophrenia. NMDAR activity is negatively regulated by some G protein–cou-pled receptors (GPCRs). Signaling through these GPCRs is reduced by Regulator of G protein Signaling 4 (RGS4). Thus, lower levels of RGS4...
Background:
Convergent findings indicate that cortical gamma-aminobutyric acid (GABA)ergic circuitry is altered in schizophrenia. Postmortem studies have consistently found lower levels of glutamic acid decarboxylase 67 (GAD67) messenger RNA (mRNA) in the prefrontal cortex (PFC) of subjects with schizophrenia. At the cellular level, the density of...
Non-overlapping groups of cortical γ-aminobutyric acid-releasing (GABAergic) neurons are identifiable by the presence of calbindin (CB), calretinin (CR), or parvalbumin (PV). Boutons from PV neuron subtypes are also distinguishable by differences in protein levels of the GABA-synthesizing enzymes GAD65 and GAD67. Multilabel fluorescence microscopy...
Cortical excitatory and inhibitory synapses are disrupted in schizophrenia, the symptoms of which often emerge during adolescence, when cortical excitatory synapses undergo pruning. In auditory cortex, a brain region implicated in schizophrenia, little is known about the development of excitatory and inhibitory synapses between early adolescence an...
Fluorescence immunocytochemistry, which in the most basic terms uses antibodies and fl uorochromes to localize specifi c proteins, has long been a cornerstone technique in the fi eld of neuroscience. Both fl uorochromes and the main tool used to visualize them, the fl uorescence microscope, have gone through major changes since the humble beginning...
Microtubule-associated protein 2 (MAP2) is a neuronal protein that plays a role in maintaining dendritic structure through its interaction with microtubules. In schizophrenia (Sz), numerous studies have revealed that the typically robust immunoreactivity (IR) of MAP2 is significantly reduced across several cortical regions. The relationship between...
Development of inhibition onto pyramidal cells may be crucial for the emergence of cortical network activity, including gamma
oscillations. In primate dorsolateral prefrontal cortex (DLPFC), inhibitory synaptogenesis starts in utero and inhibitory
synapse density reaches adult levels before birth. However, in DLPFC, the expression levels of γ-amino...
Background: Altered GABA signaling in the prefrontal cortex (PFC) has been associated with cognitive dysfunction in schizophrenia and schizoaffective disorder. PFC levels of the GABA-synthesizing enzyme glutamic acid decarboxylase 67kD (GAD67) has been consistently reported to be lower in these disorders, but the status of the second GABA-synthesiz...
Background:
Altered gamma-aminobutyric acid (GABA) signaling in the prefrontal cortex (PFC) has been associated with cognitive dysfunction in patients with schizophrenia and schizoaffective disorder. Levels of the GABA-synthesizing enzyme glutamic acid decarboxylase 67-kDa isoform (GAD67) in the PFC have been consistently reported to be lower in p...
Psychosis occurs in 40-60% of Alzheimer's disease (AD) subjects, is heritable, and indicates a more rapidly progressive disease phenotype. Neuroimaging and postmortem evidence support an exaggerated prefrontal cortical synaptic deficit in AD with psychosis. Microtubule-associated protein tau is a key mediator of amyloid-β-induced synaptotoxicity in...
Cortical circuitry dysfunction in schizophrenia has been studied at many different levels of resolution, but not at the most basic unit of network organization-synaptic inputs. Multi-label electron or confocal light microscopy is required to examine specific types of synaptic inputs, and application of these methods to quantitatively study disease-...
Dendritic spines are the site of most excitatory synapses, the loss of which correlates with cognitive impairment in patients with Alzheimer disease. Substantial evidence indicates that amyloid-β (Aβ) peptide, either insoluble fibrillar Aβ deposited into plaques or soluble nonfibrillar Aβ species, can cause spine loss but the concurrent contributio...
Schizophrenia is associated with auditory processing impairments that could arise as a result of primary auditory cortex excitatory circuit pathology. We have previously reported a deficit in dendritic spine density in deep layer 3 of primary auditory cortex in subjects with schizophrenia. As boutons and spines can be structurally and functionally...
Parvalbumin (PV)-containing cortical GABA neurons include chandelier cells (PVChCs) and basket cells (PVBCs), which innervate the axon initial segment (AIS) and soma/proximal dendrites of pyramidal cells, respectively. In monkey prefrontal cortex (PFC), the density of PVChC axon cartridges detectable by PV immunoreactivity peaks prior to the onset...
GABA (γ-aminobutyric acid)-ergic interneurons are a structurally and functionally diverse group of cells that, together, regulate the activity of neuronal networks giving rise to the brain oscillations necessary for information processing. The phenotypes of GABAergic neurons can be classified by morphological, electrophysiological, and neurochemic...
Schizophrenia is associated with perceptual and physiological auditory processing impairments that may result from primary auditory cortex excitatory and inhibitory circuit pathology. High-frequency oscillations are important for auditory function and are often reported to be disrupted in schizophrenia. These oscillations may, in part, depend on up...
Neuregulin-1 and ErbB4 are genetically associated with schizophrenia, and detailed knowledge of the cellular and subcellular localization of ErbB4 is important for understanding how neuregulin-1 regulates neuronal network activity and behavior. Expression of ErbB4 is restricted to interneurons in the rodent hippocampus and cortex. However, controve...
Cognitive deficits in schizophrenia are associated with altered activity of the dorsolateral prefrontal cortex, which has been attributed to lower expression of the 67 kDa isoform of glutamic acid decarboxylase (GAD67), the major γ-aminobutyric acid (GABA)-synthesizing enzyme. However, little is known about the relationship of prefrontal GAD67 mRNA...
Subclasses of γ-aminobutyric acid (GABA) interneurons differentially influence cortical network activity. The contribution of differences in GABA synthesis and reuptake in axon boutons to cell type-specific functions is unknown. GABA is synthesized within boutons by glutamic acid decarboxylase 65 (GAD65) and GAD67, while GAT1 is responsible for GAB...
Deficits of cognitive control in schizophrenia are associated with altered gamma oscillations in the prefrontal cortex. Paralbumin basket interneurons, which innervate the perisomatic region of pyramidal neurons, appear to play a key role in generating cortical gamma oscillations. In the prefrontal cortex of subjects with schizophrenia, alterations...
Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmiss...
Exposure to cannabis impairs cognitive functions reliant on the circuitry of the dorsolateral prefrontal cortex (DLPFC) and increases the risk of schizophrenia. The actions of cannabis are mediated via the brain cannabinoid 1 receptor (CB1R), which in rodents is heavily localized to the axon terminals of cortical GABA basket neurons that contain ch...
Converging lines of evidence indicate that schizophrenia is characterized by impairments of synaptic machinery within cerebral cortical circuits. Efforts to localize these alterations in brain tissue from subjects with schizophrenia have frequently been limited to the quantification of structures that are non-selectively identified (e.g., dendritic...
Total internal reflection fluorescence (TIRF) microscopy (TIRFM) is an elegant optical technique that provides for the excitation of fluorophores in an extremely thin axial region ("optical section"). The method is based on the principle that when excitation light is totally internally reflected in a transparent solid (e.g., coverglass) at its inte...
During neuron development, the biosynthetic needs of the axon initially outweigh those of dendrites. However, although a localized role for the early secretory pathway in dendrite development has been observed, such a role in axon growth remains undefined. We therefore studied the localization of Sar1, a small GTPase that controls ER export, during...
Little is known about the impact ectopically located neurons have on the functional connectivity of local circuits. The ApoER2 knockout mouse has subtle cytoarchitectural disruptions, altered prepulse inhibition, and memory abnormalities. We evaluated this mouse mutant as a model to study the role ectopic neurons play in the manifestation of sympto...
The heterogeneity of gamma-aminobutyric acid interneurons in the rodent neocortex is well-established, but their classification into distinct subtypes remains a matter of debate. The classification of interneurons in the primate neocortex is further complicated by a less extensive database of the features of these neurons and by reported interspeci...
Citations
... Different subtypes of inhibitory neurons target specific subcellular compartments 50 of excitatory neurons and exhibit specialized roles in regulating microcircuit function 53,[55][56][57][58][59][60] . Dysfunction in inhibitory circuits has been implicated in numerous psychiatric conditions, most prominently in schizophrenia pathophysiology 19,20,[61][62][63][64][65][66][67][68][69][70] . Therefore, understanding the role of inhibitory neurons in microcircuit dysfunction is essential for unraveling the complexity of neural networks and their contribution to various brain functions and disorders. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/11431281224979942-1708527023546_Q64/Samuel-Dienel.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/726625209569280-1550252358327_Q64/Kevin-Dowling-6.jpg)
... 55 Activation of cannabinoid receptor 1 (CB1R) in the anterior piriform cortex and hippocampus led to a decrease in inhibitory synaptic transmission. 56,57 The presynaptic CB1R, known to be highly expressed on CCK+ GABAergic neurons, [57][58][59] has the capability to suppress the co-release of CCK and GABA, thereby modulating inhibitory longterm potentiation (iLTP). Pre-synaptically targeted interneurons (e.g., CCK), can be influenced by firing activity in the post-synaptic neurons while dendritically targeted interneurons (e.g., somatostatin [SST]) are affected by the activity of glutamatergic neurons. ...
... A published study of brain tissue suggests that children with autism have a surplus of syn-apses [96]. Nagata et al. [97] also found that in mouse models of schizophrenia, extralarge synapses are over-represented, which evoked supra-linear dendritic and somatic integration, resulting in increased neuronal firing. The probability of extra-large spines correlated negatively with working memory [97]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/538821327376385-1505476423976_Q64/Kisho-Obi.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/272763944435734-1442043400752_Q64/Akiko-Hayashi-Takagi.jpg)
... This raises intracellular glutamate concentration, inducing further synaptic dysfunction and also the release of Aß from glutamatergic synapses (Sokolow et al., 2012). A loss of VGLUT1 or VGLUT2 expression has been documented in the frontal, parietal and occipital cortices in AD, which appears to correlate with the cognitive presentation of patients (Kirvell et al., 2006;Kashani et al., 2008;Mi et al., 2023). However, the regional hippocampal-specific alterations have not yet been explored. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/764757640503297-1559343838647_Q64/Michael-Malek-Ahmadi.jpg)
... In rodent models of psychosis, PCP-like drugs ultimately induce regionally specific excitotoxic damage to glutamate neurones, loss of parvalbumin containing GABA interneurons and cognitive impairment [18,19]. In humans also, post-mortem brain studies consistently report impaired function in parvalbumin and somatostatin containing subtypes of GABA interneurons [20,21]. Equally, GABA changes could be the primary driver of glutamate changes and are compatible with the long-standing GABA deficiency theory of schizophrenia [22]. ...
... For example, mPFC neurons expressing corticotropin-releasing factor receptor type 1 (CRF1 + ) were differentially altered by chronic ethanol exposure compared to neighboring CRFR1neurons (Patel et al., 2022) Importantly, findings from this study suggested that ethanol-induced neuroadaptations occurring in CRF1 + mPFC neurons likely play a role in mediating withdrawalassociated anxiety-like behavior (Patel et al., 2022). Distinct subtypes of mPFC interneurons (e.g., parvalbumin, somatostatin, VIP) are also differentially affected by chronic ethanol exposure (see Fish & Joffe, 2022 for review). In addition, recent work found that chronic ethanol exposure results in a significant increase in glutamate release onto dorsomedial PFC (i.e., PL) neurons projecting to the basolateral amygdala (McGinnis et al., 2020). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/910710276108288-1594141658547_Q64/Max-Joffe-2.jpg)
... Optical fluorescence microscopy, in particular, has emerged as a pivotal tool in this endeavor due to its ability to visualize samples in their native state with minimal invasiveness compared to electron microscopy techniques like scanning electron micrograph [3][4][5] and transmission electron microscope (TEM) [6][7][8][9]. However, the conventional fluorescence microscopies, including confocal laser scanning microscopy (CLSM) [10][11][12] and total internal reflection microscopy [13][14][15], are constrained by Abbe's diffraction limit, which restricts their ability to resolve objects closer than approximately 200 nm. To overcome this fundamental limitation, super-resolution microscopy techniques have been developed. ...
... By performing confocal immunostaining assays for GFAP, an astroglial marker, for CB1 and for nuclear proteins in layers II/III and V of the mPFC we established morphological evidence of CB1R localization in astrocytes in this speci c brain region (Fig. 1a, b & d). The wide distribution and staining pattern of CB1R in the cortical layers evaluated was aligned with the existing literature for other brain regions 43 . Speci cally, our analysis revealed a positive colocalization with CB1R, con rming its expression by astrocytes in the cortical layers examined of the mPFC (Fig. 1d). ...
... : bioRxiv preprint Recent advances are reshaping our ability to design CRE sequences with cell type-specific activity by overcoming three gaps in knowledge: (1) scalable methods to functionally characterize natural and synthetic CREs to produce generalizable insights (2) accurate 'regulatory grammar' models of how genetic sequences lead to CRE activity across cell types, and (3) the ability to repurpose predictive models for directed CRE generation. First, MPRAs can directly characterize CRE activity potential at-scale and across cell types [14][15][16][17][18][19] . Hundreds of thousands of CREs have been functionally characterized by MPRA, providing initial insights into regulatory syntax and transcriptional specificity 20-24 . ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/430596007698433-1479673496124_Q64/Easwaran-Ramamurthy-2.jpg)
... We next narrow our analysis to ask if these models are enriched for specific subtypes of GABAergic neurons, seeking to identify a subcluster(s) that mimics MSNs of the striatum, characterized by expression of BDL11B, DRD1, DRD2, and PPP1R1B (DARPP32) [46,[60][61][62]. There are five different subclusters of GABAergic neurons identified, and each model generates a different proportion of each subcluster ( Figure S2B). ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/675580596977665-1538082374509_Q64/Jing-He-75.jpg)
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1083625806278660-1635367933084_Q64/William-Stauffer-3.jpg)
