pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS. Despite its discovery over a century ago, the pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We recently demonstrated that activity in the posterior thalamus (PO) is tightly regulated by inhibitory inputs from zona incerta (ZI). Here we test the hypothesis that CPS is associated with abnormal inhibitory regulation of PO by ZI. We recorded single units from ZI and PO in animals with CPS resulting from spinal cord lesions. Consistent with our hypothesis, the spontaneous firing rate and somatosensory evoked responses of ZI neurons were lower in lesioned animals compared with sham-operated controls. In PO, neurons recorded from lesioned rats exhibited significantly higher spontaneous firing rates and greater responses to noxious and innocuous stimuli applied to the hindpaw and to the face. These changes were not associated with increased afferent drive from the spinal trigeminal nucleus or changes in the ventroposterior thalamus. Thus CPS can result from suppressed inputs from the inhibitory nucleus zona incerta to the posterior thalamus.

Although the COVID-19 pandemic has largely not clinically affected infants in neonatal intensive care units around the globe, it has affected how care is provided. Most hospitals, including their NICUs, have significantly reduced parental and family visitation privileges. From an ethical perspective, this restriction of parental visitation in settings where infectious risk is difficult to understand. No matter what the right thing to do is, NICUs are currently having to support families of their patients via different mechanisms. In this perspective, we discuss ways NICUs can support parents and families when they are home and when they are in the NICU as well as provide infants the support needed when family members are not able to visit.

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The neurotrophin brain-derived neurotrophic factor (BDNF), via activation of its receptor, tyrosine receptor kinase B (trkB), regulates a wide variety of cellular processes in the nervous system, including neuron survival and synaptic plasticity. Although the expression of BDNF is known to be Ca 2؉ -dependent, the regulation of trkB expression has not been extensively studied. Here we report that depolarization of cultured mouse cortical neurons increased the expression of the full-length, catalytically active isoform of trkB without affecting expression of the truncated isoform. This increase in protein expression was accompanied by increased levels of transcripts encoding full-length, but not truncated, trkB. Depolarization also regulated transcription of the gene, TRKB, via entry of Ca 2؉ through voltage-gated Ca 2؉ channels and subsequent activation of Ca 2؉ -responsive elements in the two TRKB promoters. Using transient transfection of neurons with TRKB promoterluciferase constructs, we found that Ca 2؉ inhibited the upstream promoter P1 but activated the downstream promoter P2. Ca 2؉ -dependent stimulation of TRKB expression requires two adjacent, non-identical CRE sites located within P2. The coordinated regulation of BDNF and trkB by Ca 2؉ may play a role in activity-dependent survival and synaptic plasticity by enhancing BDNF signaling in electrically active neurons.The neurotrophin, brain-derived neurotrophic factor (BDNF), 1 mediates numerous functions in both the developing and mature nervous systems, including the survival of postmitotic neurons, axon growth and guidance, and synaptic plasticity (1). These effects of BDNF are mediated by the tyrosine receptor kinase, trkB. Binding of BDNF to trkB initiates dimerization and trans-autophosphorylation of tyrosine residues in the intracellular domain of trkB (2). These phosphotyrosine residues act as docking sites for effector proteins that activate downstream signaling pathways, leading to the activation of protein kinase cascades, Ca 2ϩ mobilization, and gene expression, which orchestrate the cellular responses to BDNF (3). Excitatory synaptic input and the resulting elevation in intracellular [Ca 2ϩ ] have been shown to increase the synthesis and release of BDNF (4 -9). This BDNF activates trkB receptors in the same or neighboring cells to promote their survival and may also enhance synaptic plasticity (1, 10). Although trkB levels change during development and exhibit cell-specific expression patterns (11-13), very little is known about the mechanisms that regulate TRKB expression.At least four isoforms of trkB are produced by alternative splicing of the primary transcripts of the TRKB gene (14 -16). Of these, only the full-length isoform, which contains an intracellular tyrosine kinase domain, is known to be capable of mediating BDNF signaling. Three truncated isoforms (T1, T2, and T shc ), which lack the intracellular kinase domain but possess the same extracellular BDNF binding domain as fulllength receptors, can also be generated by alternativ...

Central pain syndrome (CPS) is a debilitating condition that affects a large number of patients with a primary lesion or dysfunction in the CNS, most commonly due to spinal cord injury, stroke, and multiple sclerosis lesions. The pathophysiological processes underlying the development and maintenance of CPS are poorly understood. We have recently shown, in an animal model of CPS, that neurons in the posterior thalamic nucleus (PO) have increased spontaneous and evoked activity. We also demonstrated that these changes are due to suppressed inhibitory inputs from the zona incerta (ZI). The anterior pretectal nucleus (APT) is a diencephalic nucleus that projects on both the PO and ZI, suggesting that it might be involved in the pathophysiology of CPS. Here we test the hypothesis that CPS is associated with abnormal APT activity by recording single units from APT in anesthetized rats with CPS resulting from spinal cord lesions. The firing rate of APT neurons was increased in spinal-lesioned animals, compared with sham-operated controls. This increase was due to a selective increase in firing of tonic neurons that project to and inhibit ZI and an increase in bursts in fast bursting and slow rhythmic neurons. We also show that, in normal animals, suppressing APT results in increased PO spontaneous activity and evoked responses in a subpopulation of PO neurons. Taken together, these findings suggest that APT regulates ZI inputs to PO and that enhanced APT activity during CPS contributes to the abnormally high activity of PO neurons in CPS.