Frontiers in Synaptic Neuroscience最新文献

Short-term plasticity is an important feature in the brain for shaping neural dynamics and for information processing. Short-term plasticity is known to depend on many factors including brain region, cortical layer, and cell type. Here we focus on vasoactive-intestinal peptide (VIP) interneurons (INs). VIP INs play a key disinhibitory role in cortical circuits by inhibiting other IN types, including Martinotti cells (MCs) and basket cells (BCs). Despite this prominent role, short-term plasticity at synapses to and from VIP INs is not well described. In this study, we therefore characterized the short-term plasticity at inputs and outputs of genetically targeted VIP INs in mouse motor cortex. To explore inhibitory to inhibitory (I → I) short-term plasticity at layer 2/3 (L2/3) VIP IN outputs onto L5 MCs and BCs, we relied on a combination of whole-cell recording, 2-photon microscopy, and optogenetics, which revealed that VIP IN→MC/BC synapses were consistently short-term depressing. To explore excitatory (E) → I short-term plasticity at inputs to VIP INs, we used extracellular stimulation. Surprisingly, unlike VIP IN outputs, E → VIP IN synapses exhibited heterogeneous short-term dynamics, which we attributed to the target VIP IN cell rather than the input. Computational modeling furthermore linked the diversity in short-term dynamics at VIP IN inputs to a wide variability in probability of release. Taken together, our findings highlight how short-term plasticity at VIP IN inputs and outputs is specific to synapse type. We propose that the broad diversity in short-term plasticity of VIP IN inputs forms a basis to code for a broad range of contrasting signal dynamics.

From fly to man, the Wingless (Wg)/Wnt signaling molecule is essential for both the stability and plasticity of the nervous system. The Drosophila neuromuscular junction (NMJ) has proven to be a useful system for deciphering the role of Wg in directing activity-dependent synaptic plasticity (ADSP), which, in the motoneuron, has been shown to be dependent on both the canonical and the noncanonical calcium Wg pathways. Here we show that the noncanonical planar cell polarity (PCP) pathway is an essential component of the Wg signaling system controlling plasticity at the motoneuron synapse. We present evidence that disturbing the PCP pathway leads to a perturbation in ADSP. We first show that a PCP-specific allele of disheveled (dsh) affects the de novo synaptic structures produced during ADSP. We then show that the Rho GTPases downstream of Dsh in the PCP pathway are also involved in regulating the morphological changes that take place after repeated stimulation. Finally, we show that Jun kinase is essential for this phenomenon, whereas we found no indication of the involvement of the transcription factor complex AP1 (Jun/Fos). This work shows the involvement of the neuronal PCP signaling pathway in supporting ADSP. Because we find that AP1 mutants can perform ADSP adequately, we hypothesize that, upon Wg activation, the Rho GTPases and Jun kinase are involved locally at the synapse, in instructing cytoskeletal dynamics responsible for the appearance of the morphological changes occurring during ADSP.

Electrophysiological characterization of live human tissue from epilepsy patients has been performed for many decades. Although initially these studies sought to understand the biophysical and synaptic changes associated with human epilepsy, recently, it has become the mainstay for exploring the distinctive biophysical and synaptic features of human cell-types. Both epochs of these human cellular electrophysiological explorations have faced criticism. Early studies revealed that cortical pyramidal neurons obtained from individuals with epilepsy appeared to function "normally" in comparison to neurons from non-epilepsy controls or neurons from other species and thus there was little to gain from the study of human neurons from epilepsy patients. On the other hand, contemporary studies are often questioned for the "normalcy" of the recorded neurons since they are derived from epilepsy patients. In this review, we discuss our current understanding of the distinct biophysical features of human cortical neurons and glia obtained from tissue removed from patients with epilepsy and tumors. We then explore the concept of within cell-type diversity and its loss (i.e., "neural homogenization"). We introduce neural homogenization to help reconcile the epileptogenicity of seemingly "normal" human cortical cells and circuits. We propose that there should be continued efforts to study cortical tissue from epilepsy patients in the quest to understand what makes human cell-types "human".

The synaptic cleft is the extracellular part of the synapse, bridging the pre- and postsynaptic membranes. The geometry and molecular organization of the cleft is gaining increased attention as an important determinant of synaptic efficacy. The present study by electron microscopy focuses on short-term morphological changes at the synaptic cleft under excitatory conditions. Depolarization of cultured hippocampal neurons with high K⁺ results in an increased frequency of synaptic profiles with clefts widened at the periphery (open clefts), typically exhibiting patches of membranes lined by postsynaptic density, but lacking associated presynaptic membranes (18.0% open clefts in high K⁺ compared to 1.8% in controls). Similarly, higher frequencies of open clefts were observed in adult brain upon a delay of perfusion fixation to promote excitatory/ischemic conditions. Inhibition of basal activity in cultured neurons through the application of TTX results in the disappearance of open clefts whereas application of NMDA increases their frequency (19.0% in NMDA vs. 5.3% in control and 2.6% in APV). Depletion of extracellular Ca²⁺ with EGTA also promotes an increase in the frequency of open clefts (16.6% in EGTA vs. 4.0% in controls), comparable to that by depolarization or NMDA, implicating dissociation of Ca²⁺-dependent trans-synaptic bridges. Dissociation of transsynaptic bridges under excitatory conditions may allow perisynaptic mobile elements, such as AMPA receptors to enter the cleft. In addition, peripheral opening of the cleft would facilitate neurotransmitter clearance and thus may have a homeostatic and/or protective function.