BACKGROUND: The thalamus system plays critical roles in the regulation of reversible unconsciousness induced by general anesthetics, especially the arousal stage of general anesthesia (GA). But the function of thalamus in GA-induced loss of consciousness (LOC) is little known. The thalamic reticular nucleus (TRN) is the only GABAergic neurons-composed nucleus in the thalamus, which is composed of parvalbumin (PV) and somatostatin (SST)-expressing GABAergic neurons. The anterior sector of TRN (aTRN) is indicated to participate in the induction of anesthesia, but the roles remain unclear. This study aimed to reveal the role of the aTRN in propofol and isoflurane anesthesia.
METHODS: We first set up c-Fos straining to monitor the activity variation of aTRNPV and aTRNSST neurons during propofol and isoflurane anesthesia. Subsequently, optogenetic tools were utilized to activate aTRNPV and aTRNSST neurons to elucidate the roles of aTRNPV and aTRNSST neurons in propofol and isoflurane anesthesia. Electroencephalogram (EEG) recordings and behavioral tests were recorded and analyzed. Lastly, chemogenetic activation of the aTRNPV neurons was applied to confirm the function of the aTRN neurons in propofol and isoflurane anesthesia.
RESULTS: c-Fos straining showed that both aTRNPV and aTRNSST neurons are activated during the LOC period of propofol and isoflurane anesthesia. Optogenetic activation of aTRNPV and aTRNSST neurons promoted isoflurane induction and delayed the recovery of consciousness (ROC) after propofol and isoflurane anesthesia, meanwhile chemogenetic activation of the aTRNPV neurons displayed the similar effects. Moreover, optogenetic and chemogenetic activation of the aTRN neurons resulted in the accumulated burst suppression ratio (BSR) during propofol and isoflurane GA, although they represented different effects on the power distribution of EEG frequency.
CONCLUSIONS: Our findings reveal that the aTRN GABAergic neurons play a critical role in promoting the induction of propofol- and isoflurane-mediated GA.

A common epitope (AGSFDHKKFFKACGLSGKST) of parvalbumin from 16 fish species was excavated using bioinformatics tools combined with the characterization of fish parvalbumin binding profile of anti-single epitope antibody in this study. A competitive enzyme-linked immunosorbent assay (ELISA) based on the common epitope was established with a limit of detection of 10.15 ng/mL and a limit of quantification of 49.29 ng/mL. The developed ELISA exhibited a narrow range (71% to 107%) of related cross-reactivity of 15 fish parvalbumin. Besides, the recovery, the coefficient of variations for the intra-assay and the inter-assay were 84.3% to 108.2%, 7.4% to 13.9% and 8.5% to 15.6%. Our findings provide a novel idea for the development of a broad detection method for fish allergens and a practical tool for the detection of parvalbumin of economic fish species in food samples.

OBJECTIVE: Methyl CpG-binding protein 2 (MECP2) duplication syndrome is a rare X-linked genomic disorder affecting predominantly males, which is usually manifested as epilepsy and autism spectrum disorder (ASD) comorbidity. The transgenic line MeCP2Tg1 was used for mimicking MECP2 duplication syndrome and showed autism-epilepsy co-occurrence. Previous works suggested that the excitatory/inhibitory (E/I) imbalance is a potential common mechanism for both epilepsy and ASD. The projection neurons and parvalbumin (PV) interneurons account for the majority of E/I balance in the hippocampus. Therefore, we explored how structural changes of projection and PV+ neurons occur in the hippocampus of MeCP2Tg1 mice and whether these morphological changes contribute to epilepsy susceptibility.
METHODS: We used the interneuron Designer receptors exclusively activated by designer drugs mouse model to inhibit inhibitory neurons in the hippocampus to verify the epilepsy susceptibility of MeCP2Tg1 (FVB, an inbred strain named as sensitivity to Friend leukemia virus) mice. Electroencephalograms were recorded for the definition of seizure. We performed retro-orbital injection of virus in MeCP2Tg1 (FVB):CaMKIIα-Cre (C57BL/6) mice or MeCP2Tg1:PV-Cre (C57BL/6) mice and their littermate controls to specifically label projection and PV+ neurons for structural analysis.
RESULTS: Epilepsy susceptibility was increased in MeCP2Tg1 mice. There was a reduced number of PV neurons and reduced dendritic complexity in the hippocampus of MeCP2Tg1 mice. The dendritic complexity in MeCP2Tg1 mice was increased compared to wild-type mice, and total dendritic spine density in dentate gyrus of MeCP2Tg1 mice was also increased. Total dendritic spine density was increased in CA1 of MeCP2Tg1 mice.
CONCLUSIONS: Overexpression of MeCP2 may disrupt crucial signaling pathways, resulting in decreased dendritic complexity of PV interneurons and increased dendritic spine density of projection neurons. This reciprocal modulation of excitatory and inhibitory neuronal structures associated with MeCP2 implies its significance as a potential target in the development of epilepsy and offers a novel perspective on the co-occurrence of autism and epilepsy.

Aims: the study aimed to (i) use adeno-associated virus technology to modulate parvalbumin (PV) gene expression, both through overexpression and silencing, within the hippocampus of male mice and (ii) assess the impact of PV on the metabolic pathway of glutamate and γ-aminobutyric acid (GABA). Methods: a status epilepticus (SE) mouse model was established by injecting kainic acid into the hippocampus of transgenic mice. When the seizures of mice reached SE, the mice were killed at that time point and 30 min after the onset of SE. Hippocampal tissues were extracted and the mRNA and protein levels of PV and the 65 kDa (GAD65) and 67 kDa (GAD67) isoforms of glutamate decarboxylase were assessed using real-time quantitative polymerase chain reaction and Western blot, respectively. The concentrations of glutamate and GABA were detected with high-performance liquid chromatography (HPLC), and the intracellular calcium concentration was detected using flow cytometry. Results: we demonstrate that the expression of PV is associated with GAD65 and GAD67 and that PV regulates the levels of GAD65 and GAD67. PV was correlated with calcium concentration and GAD expression. Interestingly, PV overexpression resulted in a reduction in calcium ion concentration, upregulation of GAD65 and GAD67, elevation of GABA concentration, reduction in glutamate concentration, and an extension of seizure latency. Conversely, PV silencing induced the opposite effects. Conclusion: parvalbumin may affect the expression of GAD65 and GAD67 by regulating calcium ion concentration, thereby affecting the metabolic pathways associated with glutamate and GABA. In turn, this contributes to the regulation of seizure activity.

The extracellular matrix (ECM) within the brain possesses a distinctive composition and functionality, influencing a spectrum of physiological and pathological states. Among its constituents, perineuronal nets (PNNs) are unique ECM structures that wrap around the cell body of many neurons and extend along their dendrites within the central nervous system (CNS). PNNs are pivotal regulators of plasticity in CNS, both during development and adulthood stages. Characterized by their condensed glycosaminoglycan-rich structures and heterogeneous molecular composition, PNNs not only offer neuroprotection but also participate in signal transduction, orchestrating neuronal activity and plasticity. Interfering with the PNNs in adult animals induces the reactivation of critical period plasticity, permitting modifications in neuronal connections and promoting the recovery of neuroplasticity following spinal cord damage. Interestingly, in the adult brain, PNN expression is dynamic, potentially modulating plasticity-associated states. Given their multifaceted roles, PNNs have emerged as regulators in the domains of learning, memory, addiction behaviors, and other neuropsychiatric disorders. In this review, we aimed to address how PNNs contribute to the memory processes in physiological and pathological conditions.

The inferior colliculus (IC) represents a crucial relay station in the auditory pathway, located in the midbrain\'s tectum and primarily projecting to the thalamus. Despite the identification of distinct cell classes based on various biomarkers in the IC, their specific contributions to the organization of auditory tectothalamic pathways have remained poorly understood. In this study, we demonstrate that IC neurons expressing parvalbumin (ICPV+) or somatostatin (ICSOM+) represent two minimally overlapping cell classes throughout the three IC subdivisions in mice of both sexes. Strikingly, regardless of their location within the IC, these neurons predominantly project to the primary and secondary auditory thalamic nuclei, respectively. Cell class-specific input tracing suggested that ICPV+ neurons primarily receive auditory inputs, whereas ICSOM+ neurons receive significantly more inputs from the periaqueductal gray and the superior colliculus (SC), which are sensorimotor regions critically involved in innate behaviors. Furthermore, ICPV+ neurons exhibit significant heterogeneity in both intrinsic electrophysiological properties and presynaptic terminal size compared with ICSOM+ neurons. Notably, approximately one-quarter of ICPV+ neurons are inhibitory neurons, whereas all ICSOM+ neurons are excitatory neurons. Collectively, our findings suggest that parvalbumin and somatostatin expression in the IC can serve as biomarkers for two functionally distinct, parallel tectothalamic pathways. This discovery suggests an alternative way to define tectothalamic pathways and highlights the potential usefulness of Cre mice in understanding the multifaceted roles of the IC at the circuit level.

Parvalbumin (PV) is a major allergen in fish, and traditional treatments cannot reduce its sensitization. The effects of dense-phase carbon dioxide (DPCD) treatment on the sensitization and spatial structure of PV in Trachinotus ovatus were evaluated in this study. Western blotting and indirect ELISA were used to determine the allergenicity changes and spatial conformations of PV treated by DPCD. Tris-tricine-SDS-PAGE, circular dichroism, surface hydrophobicity, endogenous fluorescence, UV spectrophotometry, free amino group, total sulfhydryl group and SEM analyses were applied to characterize PV structure. The results showed that DPCD treatment (15 MPa, 30 min, 50 °C) could reduce PV-induced allergic reactions by 39-41 %, which destroyed the normal conformational epitopes and reduced the risk of PV-induced allergy. The secondary structure changed from ordered to disordered with a decreased content of α-helical groups, while the internal hydrophobic groups were exposed. The total sulfhydryl group content decreased significantly (P < 0.05). The surface hydrophobicity and ultraviolet absorption spectrum were enhanced, and the endogenous fluorescence peak shifted to a long wavelength. Meanwhile, the content of free amino groups increased significantly (P < 0.05). This study could provide a theoretical basis and a promising technical approach for reduction of PV allergenicities.

To investigate the alteration of PV interneurons in ALS mainly focusing its dynamic changes and its relationship with motor neurons and ErbB4 signaling.
SOD1G93A mice were used as ALS model. ALS animals were divided into different groups according to birth age: symptomatic prophase (50~60 days), symptomatic phase (90~100 days), and symptomatic progression (130~140 days). Immunofluorescence was performed for measurement of PV-positive interneurons, MMP-9, ChAT, NeuN and ErbB4. RT-qPCR and western blot were used to determine the expression of PV and MMP-9.
PV expression was remarkably higher in the anterior horn of gray matter compared with posterior horn and area in the middle of gray matter in control mice. In ALS mice, PV, MMP-9 and ErbB4 levels were gradually decreased along with onset. PV, MMP-9 and ErbB4 levels in ALS mice were significantly down-regulated than control mice after onset, indicating the alteration of PV interneurons, FαMNs and ErbB4. SαMNs levels only decreased remarkably at symptomatic progression in ALS mice compared with control mice, while γMNs levels showed no significant change during whole period in all mice. MMP-9 and ErbB4 were positively correlated with PV. NRG1 treatment significantly enhanced the expression of ErBb4, PV and MMP-9 in ALS mice.
PV interneurons decrease is along with FαMNs and ErbB4 decrease in ALS mice.

The excitatory-inhibitory imbalance has been considered an important mechanism underlying stress-related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) to induce stress. The open field test and elevated plus maze test showed that IFS-exposed rats exhibited increased anxiety-like behavior. Immunofluorescence showed that IFS rats had a decreased density of GAD67-immunoreactive interneurons in the dorsal hippocampal CA1 region, while no significant change in the density of CaMKIIα-immunoreactive glutamatergic neurons was seen. We investigated the expression of different interneuron subtype markers, including parvalbumin (PV), somatostatin (SST), and calretinin (CR), and noted a marked decline in the density of PV-immunoreactive interneurons in the dorsal CA1 region of IFS rats. The perineuronal net (PNN) is a specialized extracellular matrix structure primarily around PV interneurons. We used Wisteria floribunda agglutinin lectin to label the PNNs and observed that IFS rats had an increased proportion of PNN-coated PV-positive interneurons in CA1. The number of PSD95-positive excitatory synaptic puncta on the soma of PNN-free PV-positive interneurons was significantly higher than that of PNN-coated PV-positive interneurons. Our findings suggest that the effect of IFS on the hippocampal GABAergic interneurons could be cell-type-specific. Loss of PV phenotype in the dorsal hippocampal CA1 region may contribute to anxiety in rats. The dysregulated PV-PNN relationship in CA1 after traumatic stress exposure might represent one of the neurobiological correlates of the observed anxiety-like behavior.

Dysfunction of parvalbumin (PV) neurons is closely involved in depression, however, the detailed mechanism remains unclear. Based on the previous finding that multiple endocrine neoplasia type 1 (Protein: Menin; Gene: Men1) mutation (G503D) is associated with a higher risk of depression, a Menin-G503D mouse model is generated that exhibits heritable depressive-like phenotypes and increases PV expression in brain. This study generates and screens a serial of neuronal specific Men1 deletion mice, and found that PV interneuron Men1 deletion mice (PcKO) exhibit increased cortical PV levels and depressive-like behaviors. Restoration of Menin, knockdown PV expression or inhibition of PV neuronal activity in PV neurons all can ameliorate the depressive-like behaviors of PcKO mice. This study next found that ketamine stabilizes Menin by inhibiting protein kinase A (PKA) activity, which mediates the anti-depressant function of ketamine. These results demonstrate a critical role for Menin in depression, and prove that Menin is key to the antidepressant function of ketamine.