Acomys cahirinus is a unique Rodentia species with several distinctive physiological traits, such as precocial development and remarkable regenerative abilities. These characteristics render A. cahirinus increasingly valuable for regenerative and developmental physiology studies. Despite this, the structure and postnatal development of the central nervous system in A. cahirinus have been inadequately explored, with only sporadic data available. This study is the first in a series of papers addressing these gaps. Our first objective was to characterize the structure of the main visual thalamic region, the lateral geniculate complex, using several neuronal markers (including Ca2+-binding proteins, glutamic acid decarboxylase enzyme, and non-phosphorylated domains of heavy-chain neurofilaments) to label populations of principal neurons and interneurons in adult and newborn A. cahirinus. As typically found in other rodents, we identified three subdivisions in the geniculate complex: the dorsal and ventral lateral geniculate nuclei (LGNd and LGNv) and the intergeniculate leaflet (IGL). Additionally, we characterized internal diversity in the LGN nuclei. The \"shell\" and \"core\" regions of the LGNd were identified using calretinin in adults and newborns. In adults, the inner and outer parts of the LGNv were identified using calbindin, calretinin, parvalbumin, GAD67, and SMI-32, whereas in newborns, calretinin and SMI-32 were employed for this purpose. Our findings revealed more pronounced developmental changes in LGNd compared to LGNv and IGL, suggesting that LGNd is less mature at birth and more influenced by visual experience.

UNASSIGNED: Dysfunction of the cortico-basal circuitry - including its primary input nucleus, the striatum - contributes to neuropsychiatric disorders, such as autism and Tourette Syndrome (TS). These conditions show marked sex differences, occurring more often in males than in females. Regulatory interneurons, such as cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females. Here we investigate sex differences in the density and distribution of striatal interneurons.
UNASSIGNED: We use stereological quantification of CINs, FSIs, and somatostatin-expressing (SOM) GABAergic interneurons in the dorsal striatum (caudate-putamen) and the ventral striatum (nucleus accumbens) in male and female mice.
UNASSIGNED: Males have a higher density of CINs than females, especially in the dorsal striatum; females have equal distribution between dorsal and ventral striatum. FSIs showed similar distributions, with a greater dorsal-ventral density gradient in males than in females. SOM interneurons were denser in the ventral than in the dorsal striatum, with no sex differences.
UNASSIGNED: These sex differences in the density and distribution of FSIs and CINs may contribute to sex differences in basal ganglia function, particularly in the context of psychopathology.

The prefrontal cortex (PFC) undergoes a protracted maturation process. This is true both for local interneurons and for innervation from midbrain dopaminergic (mDA) neurons. In the striatum, dopaminergic (DA) neurotransmission is required for the maturation of medium spiny neurons during a critical developmental period. To investigate whether DA innervation influences the maturation of interneurons in the PFC, we used a conditional knockout (cKO) mouse model in which innervation from mDA neurons to the mPFC (mesoprefrontal innnervation) is not established during development. In this mouse model, the maturation of parvalbumin (PV) and calbindin (CB) interneuron populations in the PFC is dysregulated during a critical period in adolescence with changes persisting into adulthood. PV interneurons are particularly vulnerable to lack of mesoprefrontal input, showing an inability to maintain adequate PV expression with a concomitant decrease in Gad1 expression levels. Interestingly, lack of mesoprefrontal innervation does not appear to induce compensatory changes such as upregulation of DA receptor expression in PFC neurons or increased innervation density of other neuromodulatory (serotonergic and noradrenergic) innervation. In conclusion, our study shows that adolescence is a sensitive period during which mesoprefrontal input plays a critical role in promoting the maturation of specific interneuron subgroups. The results of this study will help to understand how a dysregulated mesoprefrontal DA system contributes to the pathophysiology of neurodevelopmental disorders.

The basolateral amygdala plays pivotal roles in the regulation of fear and anxiety and these processes are profoundly modulated by different neuromodulatory systems that are recruited during emotional arousal. Recent studies suggest activities of BLA interneurons and inhibitory synaptic transmission in BLA principal cells are regulated by neuromodulators to influence the output and oscillatory network states of the BLA, and ultimately the behavioral expression of fear and anxiety. In this review, we first summarize a cellular mechanism of stress-induced anxiogenesis mediated by the interaction of glucocorticoid and endocannabinoid signaling at inhibitory synapses in the BLA. Then we discuss cell type-specific activity patterns induced by neuromodulators converging on the Gq signaling pathway in BLA perisomatic parvalbumin-expressing (PV) and cholecystokinin-expressing (CCK) basket cells and their effects on BLA network oscillations and fear learning.

Parvalbumin-expressing (PV) neurons, classified by their expression of the calcium-binding protein parvalbumin, play crucial roles in the function and plasticity of the lateral habenular nucleus (LHb). This study aimed to deepen our understanding of the LHb by collecting information about the heterogeneity of LHb PV neurons in mice. To achieve this, we investigated the proportions of the transmitter machinery in LHb PV neurons, including GABAergic, glutamatergic, serotonergic, cholinergic, and dopaminergic neurotransmitter markers, using transcriptome analysis, mRNA in situ hybridization chain reaction, and immunohistochemistry. LHb PV neurons comprise three subsets: glutamatergic, GABAergic, and double-positive for glutamatergic and GABAergic machinery. By comparing the percentages of the subsets, we found that the LHb was topographically organized anteroposteriorly; the GABAergic and glutamatergic PV neurons were preferentially distributed in the anterior and posterior LHb, respectively, uncovering the anteroposterior topography of the LHb. In addition, we confirmed the mediolateral topography of lateral GABAergic PV neurons. These findings suggest that PV neurons play distinct roles in different parts of the LHb along the anteroposterior and mediolateral axes, facilitating the topographic function of the LHb. It would be interesting to determine whether their topography is differentially involved in various cognitive and motivational processes associated with the LHb, particularly the involvement of posterior glutamatergic PV neurons.

Glial cell line-derived neurotrophic factor (GDNF) is among the strongest dopamine neuron function- and survival-promoting factors known. Due to this reason, it has clinical relevance in dopamine disorders such as Parkinson\'s disease and schizophrenia. In the striatum, GDNF is exclusively expressed in interneurons, which make up only about 0.6% of striatal cells. Despite clinical significance, histological analysis of striatal GDNF system arborization and relevance to incoming dopamine axons, which bear its receptor RET, has remained enigmatic. This is mainly due to the lack of antibodies able to visualize GDNF- and RET-positive cellular processes; here, we overcome this problem by using knock-in marker alleles. We find that GDNF neurons chemoattract RET+ axons at least seven times farther in distance than medium spiny neurons (MSNs), which make up 95% of striatal neurons. Furthermore, we provide evidence that tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, is enriched towards GDNF neurons in the dopamine axons. Finally, we find that GDNF neuron arborizations occupy approximately only twelve times less striatal volume than 135 times more abundant MSNs. Collectively, our results improve our understanding of how endogenous GDNF affects striatal dopamine system function.

Spinal cord dorsal horn inhibition is critical to the processing of sensory inputs, and its impairment leads to mechanical allodynia. How this decreased inhibition occurs and whether its restoration alleviates allodynic pain are poorly understood. Here, we show that a critical step in the loss of inhibitory tone is the change in the firing pattern of inhibitory parvalbumin (PV)-expressing neurons (PVNs). Our results show that PV, a calcium-binding protein, controls the firing activity of PVNs by enabling them to sustain high-frequency tonic firing patterns. Upon nerve injury, PVNs transition to adaptive firing and decrease their PV expression. Interestingly, decreased PV is necessary and sufficient for the development of mechanical allodynia and the transition of PVNs to adaptive firing. This transition of the firing pattern is due to the recruitment of calcium-activated potassium (SK) channels, and blocking them during chronic pain restores normal tonic firing and alleviates chronic pain. Our findings indicate that PV is essential for controlling the firing pattern of PVNs and for preventing allodynia. Developing approaches to manipulate these mechanisms may lead to different strategies for chronic pain relief.

Neuronal regulation of cerebrovasculature underlies brain imaging techniques reliant on cerebral blood flow (CBF) changes. However, interpreting these signals requires understanding their neural correlates. Parvalbumin (PV) interneurons are crucial in network activity, but their impact on CBF is not fully understood. Optogenetic studies show that stimulating cortical PV interneurons induces diverse CBF responses, including rapid increases, decreases, and slower delayed increases. To clarify this relationship, we measured hemodynamic and neural responses to optogenetic stimulation of PV interneurons expressing Channelrhodopsin-2 during evoked and ongoing resting-state activity in the somatosensory cortex of awake mice. Two-photon microscopy (2P) Ca2+ imaging showed robust activation of PV-positive (PV+) cells and inhibition of PV-negative (PV-) cells. Prolonged PV+ cell stimulation led to a delayed, slow CBF increase, resembling a secondary peak in the CBF response to whisker stimulation. 2P vessel diameter measurements revealed that PV+ cell stimulation induced rapid arterial vasodilation in superficial layers and delayed vasodilation in deeper layers. Ongoing activity recordings indicated that both PV+ and PV- cell populations modulate arterial fluctuations at rest, with PV+ cells having a greater impact. These findings show that PV interneurons generate a complex depth-dependent vascular response, dominated by slow vascular changes in deeper layers.

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. Here, we observed that activation or inactivation of PVNs functioned like a volume knob in the mouse auditory cortex (ACtx), turning neural and behavioral classification of sound level up or down over a 20dB range. PVN loudness adjustments were \"sticky\", such that a single bout of 40Hz PVN stimulation sustainably suppressed ACtx sound responsiveness, potentiated feedforward inhibition, and behaviorally desensitized mice to loudness. Sensory sensitivity is a cardinal feature of autism, aging, and peripheral neuropathy, prompting us to ask whether PVN stimulation can persistently desensitize mice with ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity triggered by cochlear sensorineural damage. We found that a single 16-minute bout of 40Hz PVN stimulation session restored normal loudness perception for one week, showing that perceptual deficits triggered by irreversible peripheral injuries can be reversed through targeted cortical circuit interventions.

Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABAA and metabotropic GABAB receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABAA receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABAA, Gabra1; GABAB, Gabbr1b) in pyramidal neurons, and an enzyme that mediates GABA synthesis (GAD65) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABAB receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABAB receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders.