Frontiers in Neural Circuits最新文献

Blood flow restriction (BFR) is a peripheral intervention that induces transient and reversible physiological perturbations. While this intervention offers a unique model to explore neuromuscular responses in multiple contexts, its impact on neural input to motoneurons remains unclear. Here, the influence of BFR on muscle force control, behavior, and neural input to motoneurons during isometric-trapezoidal and isometric-sinusoidal little finger abduction precision tasks has been studied. Sixteen healthy participants performed the tasks under pre-BFR, during BFR, and at two post-BFR conditions. High-density surface electromyography (EMG) was recorded from the abductor digiti minimi muscle, and motor unit spike trains (MUST) were decomposed using blind source separation technique. Coherence between cumulative spike trains (CSTs) of identified motor units was calculated to assess common synaptic input in the delta and alpha frequency bands. As expected, during BFR application, participants reported higher level of discomfort and significant deterioration in force-tracking performance, as measured using root mean square error (RMSE). Following the BFR release, the level of discomfort, along with impaired neuromuscular performance were reduced to pre-BFR condition. Coherence analysis revealed a prominent peak in the alpha band. The mean z-score coherence in the alpha band showed a reduction of 27% for isometric-trapezoidal and 31% for isometric-sinusoidal conditions from pre-BFR to BFR, followed by a rebound post-BFR intervention with increases of 13% and 20%, respectively. In the delta band, coherence values were consistently higher during sinusoidal tasks compared to trapezoidal ones. These findings indicate that brief BFR application led to decrease in motoneuron synchronization and force control precision likely due to desensitization as shown by changes in coherence alpha band.

Cholinergic septohippocampal projections originating from the medial septal area (MSA) play a critical role in regulating attention, memory formation, stress responses, and synaptic plasticity. Cholinergic axons from the MSA extensively innervate all hippocampal regions, providing a structural basis for the simultaneous release of acetylcholine (ACh) across the entire hippocampus. However, this widespread release appears inconsistent with the specific functional roles that ACh is thought to serve during distinct behaviors. A key unresolved question is how the dynamics of ACh tissue concentrations determine its ability to activate different receptor types and coordinate individual synaptic pathways. Here, we highlight several debated issues, including the potential intrinsic source of ACh within the hippocampus - such as cholinergic interneurons - and the co-release of ACh with GABA. Furthermore, we discuss recent findings on in vivo ACh concentration dynamics, which present a new dilemma for understanding ACh signaling in the hippocampus: the contrast between "global" ACh release, driven by synchronous activation of MSA neurons, and "local" release, which may be influenced by yet unidentified factors.

In the mammalian olfactory bulb (OB), gap junctions coordinate synchronous activity among mitral and tufted cells to process olfactory information. In insects, gap junctions are also present in the antennal lobe (AL), a structure homologous to the mammalian OB. The invertebrate gap junction protein ShakB contributes to electrical synapses between AL projection neurons (PNs) in Drosophila. Other gap junction proteins, including innexin 7 (Inx7), are also expressed in the Drosophila AL, but little is known about their contribution to intercellular communication during olfactory information processing. In this study, we report spontaneous calcium transients in PNs grown in cell culture that are highly synchronous when these neurons are physically connected. RNAi-mediated knockdown of Inx7 in cultured PNs blocks calcium transient neuronal synchronization. In vivo, downregulation of Inx7 in the AL impairs both vinegar-induced electrophysiological calcium responses and behavioral responses to this appetitive stimulus. These results demonstrate that Inx7-encoded gap junctions functionally coordinate PN activity and modulate olfactory information processing in the adult Drosophila AL.

As the core area of emotion regulation, the amygdala is involved in and regulates many related behaviors, such as fear, anxiety, depression, as well as reward, learning, and memory. Most previous connectional studies have focused on the anterior and middle parts of the basolateral nucleus (BL) and basomedial nucleus (BM) of the amygdala. Little is known about the brain-wide connections of the posterior part of the BL and BM (termed parvicellular subdivision of the BL and BM, i.e., BLpc and BMpc). In this study, brain-wide afferent and efferent projections of the BLpc and BMpc in the rats are investigated using both retrograde and anterograde tracing methods. Both common and differential connections of the BLpc and BMpc are revealed. Major common inputs of both regions originate from the ventral hippocampal CA1 and prosubiculum, sublenticular extended amygdala, anterior basomedial nucleus, midline thalamic nuclei, endopiriform nucleus, dorsal raphe, piriform cortex and lateral entorhinal cortex. The BLpc receives preferential inputs from agranular insular cortex, amygdalopiriform transition area, periaqueductal gray, parataenial nucleus and anterior cortical nucleus of the amygdala. The BMpc preferentially receives its inputs from the peripeduncular nucleus, paraventricular nucleus of thalamus, ventromedial hypothalamic nucleus (VMH), caudal bed nucleus of stria terminalis (BST), medial amygdaloid nucleus and posterior cortical nucleus of the amygdala. Major differential outputs of the BLpc and BMpc are also obvious. The BLpc projects mainly to nucleus accumbens, rostral BST, lateral central amygdaloid nucleus (Ce), intermediate BL and BM. The BMpc sends its main outputs to VMH, medial Ce, caudal BST, prosubiculum, and perirhinal-ectorhinal cortices. These major findings are further confirmed with anterograde viral tracing in mice. Compared with previous findings in monkeys, our findings in rodents suggest that the BLpc and BMpc have overall similar connectional patterns across species. In addition, some gene markers for BM subdivisions are identified. All these findings would provide an important anatomical basis for the understanding of emotion-related neuronal circuits and diseases and for cross-species comparison of the subcircuits in amygdaloid complex.

Vagus nerve stimulation (VNS) has emerged as a promising therapeutic intervention across various neurological and psychiatric conditions, including epilepsy, depression, and stroke rehabilitation; however, its mechanisms of action on neural circuits remain incompletely understood. Here, we present a novel theoretical framework based on predictive coding that conceptualizes VNS effects through differential modulation of feedforward and feedback neural circuits. Based on recent evidence, we propose that VNS shifts the balance between feedforward and feedback processing through multiple neuromodulatory systems, resulting in enhanced feedforward signal transmission. This framework integrates anatomical pathways, receptor distributions, and physiological responses to explain the influence of the VNS on neural dynamics across different spatial and temporal scales. Vagus nerve stimulation may facilitate neural plasticity and adaptive behavior through acetylcholine and noradrenaline (norepinephrine), which differentially modulate feedforward and feedback signaling. This mechanistic understanding serves as a basis for interpreting the cognitive and therapeutic outcomes across different clinical conditions. Our perspective provides a unified theoretical framework for understanding circuit-specific VNS effects and suggests new directions for investigating their therapeutic mechanisms.

Neural firing rates are thought to represent values which code information. There are drawbacks with using biophysical events to represent numbers. (1) Rate code (like any sequence) is inherently slow to read. (2) At short intervals, the code becomes unintelligible biophysical noise. (3) Transmission times. The vital contribution of the cerebellum to skilled execution and coordination of movements requires precision timing. We present a theory supported by modeling that the output cell group of the cerebellar network is a practical solution to timing problems. In this role, it converts irregularly-patterned firing of Purkinje cells into an effectively instantaneous rate received by output cells, transforms the rate into linear analog modulation of output cell firing, synchronizes firing between output cells, and compensates for lag caused by extracerebellar transmission times. The cerebellum is widely connected to the midbrain and the cerebral cortex and involved in cognitive functions. Modular network wiring suggests that the cerebellum may perform the same computation on input from all sources regardless of where it is from. If so, and the deep cerebellar nuclei make the same contribution to the role of the cerebellum in other functions, an understanding of motor function would also provide insight into the substrate of cognitive functions.

The orbitofrontal cortex (ORB) exhibits a complex structure and diverse functional roles, including emotion regulation, decision-making, and reward processing. Structurally, it comprises three distinct regions: the medial part (ORBm), the ventrolateral part (ORBvl), and the lateral part (ORBl), each with unique functional attributes, such as ORBm's involvement in reward processing, ORBvl's regulation of depression-like behavior, and ORBl's response to aversive stimuli. Dysregulation of the ORB has been implicated in various psychiatric disorders. However, the neurocircuitry underlying the functions and dysfunctions of the ORB remains poorly understood. This study employed recombinant adeno-associated viruses (rAAV) and rabies viruses with glycoprotein deletion (RV-ΔG) to retrogradely trace monosynaptic inputs to three ORB subregions in male C57BL/6J mice. Inputs were quantified across the whole brain using fluorescence imaging and statistical analysis. Results revealed distinct input patterns for each ORB subregion, with significant contributions from the isocortex and thalamus. The ORBm received prominent inputs from the prelimbic area, agranular insular area, and hippocampal field CA1, while the ORBvl received substantial intra-ORB inputs. The ORBl exhibited strong inputs from the somatomotor and somatosensory areas. Thalamic inputs, particularly from the mediodorsal nucleus and submedial nucleus of the thalamus, were widespread across all ORB subregions. These findings provide novel insights into the functional connectivity of ORB subregions and their roles in neural circuit mechanisms underlying behavior and psychiatric disorders.

[This corrects the article DOI: 10.3389/fncir.2024.1463941.].

The prefrontal cortex (PFC), located at the anterior region of the cerebral cortex, is a multimodal association cortex essential for higher-order brain functions, including decision-making, attentional control, memory processing, and regulation of social behavior. Structural, circuit-level, and functional abnormalities in the PFC are often associated with neurodevelopmental disorders. Here, we review recent findings on the postnatal development of the PFC, with a particular emphasis on rodent studies, to elucidate how its structural and circuit properties are established during critical developmental windows and how these processes influence adult behaviors. Recent evidence also highlights the lasting effects of early life stress on the PFC structure, connectivity, and function. We explore potential mechanisms underlying these stress-induced alterations, with a focus on epigenetic regulation and its implications for PFC maturation and neurodevelopmental disorders. By integrating these insights, this review provides an overview of the developmental processes shaping the PFC and their implications for brain health and disease.