Neuroscience
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Spreading depolarization (SD) is a slowly propagating wave of prolonged activation followed by a period of synaptic suppression. Some prior reports have shown potentiation of synaptic transmission after recovery from synaptic suppression and noted similarities with the phenomenon of long-term potentiation (LTP). Since SD is increasingly recognized as participating in diverse neurological disorders, it is of interest to determine whether SD indeed leads to a generalized and sustained long-term strengthening of synaptic connections. ⋯ Potentiation was saturated after a single SD and adenosine A1 receptor activation did not mask additional potentiation. Induction of LTP with theta-burst stimulation was not altered by prior induction of SD and molecular mediators known to block LTP induction did not block SD-induced potentiation. Together, these results indicate an intermediate duration potentiation that is distinct from hippocampal LTP and may have implications for circuit function for 1-2 h following SD.
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Memory consolidation refers to a process by which labile newly formed memory traces are progressively strengthened into long term memories and become more resistant to interference. Recent work has revealed that spontaneous hippocampal activity during rest, commonly referred to as "offline" activity, plays a critical role in the process of memory consolidation. Hippocampal reactivation occurs during sharp-wave ripples (SWRs), which are events associated with highly synchronous neural firing in the hippocampus and modulation of neural activity in distributed brain regions. ⋯ In this review, we further describe how SWRs, ripples and slow oscillations are affected in Alzheimer's disease, epilepsy, and schizophrenia. We then compare the differences of neuronal reactivation and discuss how different reactivation abnormalities cause pathological changes in these diseases. Aberrant neural reactivation provides insights into disease pathogenesis and may even serve as biomarkers for early disease progression and treatment response.
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APOE ε4 is risk for cognitive decline even in normal aging, but its effect on the whole-brain functional connectivity (FC) among time in young adults remain elusive. This study aimed to validate the time-by-APOE ε4 interaction on brain FC of this specific population. Longitudinal changes in neuropsychological assessments and resting-state functional magnetic resonance imaging in 26 ε4 carriers and 26 matched non-ε4 carriers were measured for about 3 years. ⋯ The main effect of gene showed ε4 carriers has lower FC between left TG and right middle frontal gyrus as compared with non-ε4 both at baseline and follow-up study; ε4 carriers has lower FC between left TG and right supramarginal as compared with non-ε4 at baseline, but no difference in follow-up study. The time-by-APOE ε4 interaction on brain FC was demonstrated at a young age, and left TG was the earliest affected brain regions. The young adult ε4 carriers experience decreased FC among time in the absence overt clinical symptoms.
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Functioning of the nervous system requires proper formation and specification of neurons as well as accurate connectivity and signalling between them. Locomotor behaviour depends upon these events that occur during neural development, and any aberration in them could result in motor disorders. Transcription factors are believed to be master regulators that control these processes, but very few linked to behaviour have been identified so far. ⋯ All Cph-expressing neurons in the ventral nerve cord are glutamatergic. Our results imply that Cph modulates primary locomotor activity through configuration of glutamatergic neurons. Thus, this study ascribes a hitherto unknown role to Cph in locomotor behaviour of Drosophila melanogaster.
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The dorsal motor nucleus of the vagus (DMV) contains parasympathetic motoneurons that project to the heart and lungs. These motoneurons control ventricular excitability/contractility and airways secretions/blood flow, respectively. However, their electrophysiological properties, morphology and synaptic input activity remain unknown. ⋯ These differences were in part due to highly branched dendritic complexity and lower magnitude of A-type K+ currents. By evaluating expression of channels that mediate A-type currents from single motoneurons, we demonstrated a lower level of Kv4.2 in pulmonary versus cardiac motoneurons, whereas Kv4.3 and Kv1.4 levels were similar. Thus, with the distinct electrical, morphological, and molecular properties of DMV cardiac and pulmonary motoneurons, we surmise that these cells offer a new vista of opportunities for genetic manipulation providing improvement of parasympathetic function in cardiorespiratory diseases such heart failure and asthma.