Organization of corticocortical and thalamocortical top-down inputs in the primary visual cortex.

Unified visual perception requires integration of bottom-up and top-down inputs in the primary visual cortex (V1), yet the organization of top-down inputs in V1 remains unclear. Here, we used optogenetics-assisted circuit mapping to identify how multiple top-down inputs from higher-order cortical and thalamic areas engage V1 excitatory and inhibitory neurons. Top-down inputs overlap in superficial layers yet segregate in deep layers. Inputs from the medial secondary visual cortex (V2M) and anterior cingulate cortex (ACA) converge on L6 Pyrs, whereas ventrolateral orbitofrontal cortex (ORBvl) and lateral posterior thalamic nucleus (LP) inputs are processed in parallel in Pyr-type-specific subnetworks (Pyr←ORBvl and Pyr←LP) and drive mutual inhibition between them via local interneurons. Our study deepens understanding of the top-down modulation mechanisms of visual processing and establishes that V2M and ACA inputs in L6 employ integrated processing distinct from the parallel processing of LP and ORBvl inputs in L5.

A frontal transcallosal inhibition loop mediates interhemispheric balance in visuospatial processing.

Interhemispheric communication through the corpus callosum is required for both sensory and cognitive processes. Impaired transcallosal inhibition causing interhemispheric imbalance is believed to underlie visuospatial bias after frontoparietal cortical damage, but the synaptic circuits involved remain largely unknown. Here, we show that lesions in the mouse anterior cingulate area (ACA) cause severe visuospatial bias mediated by a transcallosal inhibition loop. In a visual-change-detection task, ACA callosal-projection neurons (CPNs) were more active with contralateral visual field changes than with ipsilateral changes. Unilateral CPN inactivation impaired contralateral change detection but improved ipsilateral detection by altering interhemispheric interaction through callosal projections. CPNs strongly activated contralateral parvalbumin-positive (PV+) neurons, and callosal-input-driven PV+ neurons preferentially inhibited ipsilateral CPNs, thus mediating transcallosal inhibition. Unilateral PV+ neuron activation caused a similar behavioral bias to contralateral CPN activation and ipsilateral CPN inactivation, and bilateral PV+ neuron activation eliminated this bias. Notably, restoring interhemispheric balance by activating contralesional PV+ neurons significantly improved contralesional detection in ACA-lesioned animals. Thus, a frontal transcallosal inhibition loop comprising CPNs and callosal-input-driven PV+ neurons mediates interhemispheric balance in visuospatial processing, and enhancing contralesional transcallosal inhibition restores interhemispheric balance while also reversing lesion-induced bias.

Hypokalemic periodic paralysis presenting as asymmetric focal flaccid paralysis: A case report and literature review.

Patients with the most common form of hypokalemic periodic paralysis (HypoKPP) exhibit symmetrical limb weakness. However, few patients present with asymmetric limb weakness. Here, we describe a unique case of HypoKPP presenting as asymmetric focal flaccid paralysis. In addition, a literature review is performed to provide a perspective for clinical management of similar cases. We present a detailed characterization of this rare type of HypoKPP. The initial presentation was right hand weakness, which progressed to bilateral lower limb weakness. Neurological examination showed that the affected muscles were uniquely confined to specific nerve innervation, i.e., right distal median nerve-innervated muscle, right deep peroneal nerve-innervated muscle and left side. The patient's serum level of potassium was lower than normal; the decline of long exercise test (LET) was higher than normal range; neurophysiological assessment revealed low amplitude compound muscle action potential (CMAP) during attack, the CMAP and patient's weakness rapidly returned to normal level after potassium supplementation. Therefore, HypoKPP can be formally diagnosed based on neurological examination, medical history, timely neural electrophysiological examinations and measurement of blood potassium level.

Adenosine-independent regulation of the sleep-wake cycle by astrocyte activity.

Astrocytes play a crucial role in regulating sleep-wake behavior, and adenosine signaling is generally thought to be involved. Here we show multiple lines of evidence supporting that modulation of the sleep-wake behavior by astrocyte Ca2+ activity could occur without adenosine signaling. In the basal forebrain and the brainstem, two brain regions that are known to be essential for sleep-wake regulation, chemogenetically-induced astrocyte Ca2+ elevation significantly modulated the sleep-wake cycle. Although astrocyte Ca2+ level positively correlated with the amount of extracellular adenosine, as revealed by a genetically encoded adenosine sensor, we found no detectable change in adenosine level after suppressing astrocyte Ca2+ elevation, and transgenic mice lacking one of the major extracellular ATP-adenosine conversion enzymes showed similar extracellular adenosine level and astrocyte Ca2+-induced sleep modulation. Furthermore, astrocyte Ca2+ is dependent primarily on local neuronal activity, causing brain region-specific regulation of the sleep-wake cycle. Thus, neural activity-dependent astrocyte activity could regulate the sleep-wake behavior independent of adenosine signaling.

Long-segment spinal cord infarction complicated with multiple cerebral infarctions: a case report.

BACKGROUND: Spinal cord infarction is a rare disorder, constituting only 1% to 2% of all neurological vascular emergencies (making it less frequent than ischaemic brain injury); however, it is severe. A case of long-segment spinal cord infarction complicated with multiple cerebral infarctions has not been reported to date. CASE PRESENTATION: Here, we describe one such case: a patient with spinal cord infarction from the cervical 7 (C7) to thoracic 6 (T6) vertebrae, along with anterior spinal artery syndrome and complicated by multiple cerebral infarctions. A 65-year-old farmer experienced sudden onset of severe pain in his chest, back and upper limbs while unloading heavy objects. Subsequently, both his lower limbs became weak and hypoaesthetic, and he was unable to walk. Spinal magnetic resonance imaging (MRI) revealed equal T1 and long T2 signals centred on the anterior horn of the spinal cord. The axial slice of these signals was shaped like an owl's eye. After receiving drug treatment and active rehabilitation treatment, the patient's ability to walk was restored. CONCLUSIONS: Long-segment spinal cord infarction is rare and can be complicated with cerebral infarction. The specific aetiology is worth exploring.

Spontaneous changes in brain striatal dopamine synthesis and storage dynamics ex vivo reveal end-product feedback-inhibition of tyrosine hydroxylase.

Synaptic events are important to define treatment strategies for brain disorders. In the present paper, freshly obtained rat brain striatal minces were incubated under different times and conditions to determine dopamine biosynthesis, storage, and tyrosine hydroxylase phosphorylation. Remarkably, we found that endogenous dopamine spontaneously accumulated during tissue incubation at 37 °C ex vivo while dopamine synthesis simultaneously decreased. We analyzed whether these changes in brain dopamine biosynthesis and storage were linked to dopamine feedback inhibition of its synthesis-limiting enzyme tyrosine hydroxylase. The aromatic-l-amino-acid decarboxylase inhibitor NSD-1015 prevented both effects. As expected, dopamine accumulation was increased with l-DOPA addition or VMAT2-overexpression, and dopamine synthesis decreased further with added dopamine, the VMAT2 inhibitor tetrabenazine or D2 auto-receptor activation with quinpirole, accordingly to the known synaptic effects of these treatments. Phosphorylation activation and inhibition of tyrosine hydroxylase on Ser31 and Ser40 with okadaic acid, Sp-cAMP and PD98059 also exerted the expected effects. However, no clear-cut association was found between dopamine feedback inhibition of its own biosynthesis and changes of tyrosine hydroxylase phosphorylation, assessed by Western blot and mass spectrometry. The later technique also revealed a new Thr30 phosphorylation in rat tyrosine hydroxylase. Our methodological assessment of brain dopamine synthesis and storage dynamics ex vivo could be applied to predict the in vivo effects of pharmacological interventions in animal models of dopamine-related disorders.

A cortico-collicular pathway for motor planning in a memory-dependent perceptual decision task.

Survival in a dynamic environment requires animals to plan future actions based on past sensory evidence, known as motor planning. However, the neuronal circuits underlying this crucial brain function remain elusive. Here, we employ projection-specific imaging and perturbation methods to investigate the direct pathway linking two key nodes in the motor planning network, the secondary motor cortex (M2) and the midbrain superior colliculus (SC), in mice performing a memory-dependent perceptual decision task. We find dynamic coding of choice information in SC-projecting M2 neurons during motor planning and execution, and disruption of this information by inhibiting M2 terminals in SC selectively impaired decision maintenance. Furthermore, we show that while both excitatory and inhibitory SC neurons receive synaptic inputs from M2, these SC subpopulations display differential temporal patterns in choice coding during behavior. Our results reveal the dynamic recruitment of the premotor-collicular pathway as a circuit mechanism for motor planning.

Hierarchy in sensory processing reflected by innervation balance on cortical interneurons.

Sensory processing is subjected to modulation by behavioral contexts that are often mediated by long-range inputs to cortical interneurons, but their selectivity to different types of interneurons remains largely unknown. Using rabies-virus tracing and optogenetics-assisted recording, we analyzed the long-range connections to various brain regions along the hierarchy of visual processing, including primary visual cortex, medial association cortices, and frontal cortices. We found that hierarchical corticocortical and thalamocortical connectivity is reflected by the relative weights of inputs to parvalbumin-positive (PV+) and vasoactive intestinal peptide-positive (VIP+) neurons within the conserved local circuit motif, with bottom-up and top-down inputs preferring PV+ and VIP+ neurons, respectively. Our algorithms based on innervation weights for these two types of local interneurons generated testable predictions of the hierarchical position of many brain areas. These results support the notion that preferential long-range inputs to specific local interneurons are essential for the hierarchical information flow in the brain.

Kir4.1 channels in NG2-glia play a role in development, potassium signaling, and ischemia-related myelin loss.

The contribution of the inwardly rectifying K+ channel subtype Kir4.1 has been focused mainly on astrocytes, where they play important roles in the maintenance of resting membrane potential, extracellular K+ uptake, and facilitation of glutamate uptake in the central nervous system. Here, we report the role of Kir4.1 channels in NG2-glia during brain development, potassium signaling, and in an ischemic stroke disease model. Kir4.1 channels are widely expressed in NG2-glia during brain development. In the adult mouse hippocampus, Kir4.1 channels in NG2-glia constitute more than 80% of K+ channels inward currents. This large portion of Kir4.1 channel currents exhibits a deficit in NG2-glia as an initial response in a transient ischemic mouse model. Further evidence indicates that Kir4.1 deficits in NG2-glia potentially cause axonal myelin loss in ischemia through the association with oligodendrocyte-specific protein (OSP/Claudin-11), which unravels a potential therapeutic target in the treatment of ischemic stroke.

Roles of NG2-glia in ischemic stroke.

Recent studies have shown that a widely distributed class of glial cells, termed NG2-glia, engages in rapid signaling with surrounding neurons through direct synaptic contacts in the developing and mature central nervous system (CNS). This unique glial cell group has a typical function of proliferating and differentiating into oligodendrocytes during early development of the brain, which is crucial to axon myelin formation. Therefore, NG2-glia are also called oligodendrocyte precursor cells (OPCs). In vitro and in vivo studies reveal that NG2-glia expressing receptors and ion channels demonstrate functional significance for rapid signaling with neuronal synapses and modulation of neuronal activities in both physiological and pathological conditions. Although it is well known that NG2-glia play an important role in demyelinating diseases such as multiple sclerosis, little is known about how NG2-glia or OPCs impact neurons and brain function following ischemic injury. This review summarizes recent progress on the roles of NG2-glia in ischemic stroke and illustrates new approaches for targeting NG2-glia in the brain to treat this disease.