Myelination and Isochronicity in Neural Networks

Our brain contains a multiplicity of neuronal networks. In many of these, information sent from presynaptic neurons travels through a variety of pathways of different distances, yet arrives at the postsynaptic cells at the same time. Such isochronicity is achieved either by changes in the conduction velocity of axons or by lengthening the axonal path to compensate for fast conduction. To regulate the conduction velocity, a change in the extent of myelination has recently been proposed in thalamocortical and other pathways. This is in addition to a change in the axonal diameter, a previously identified, more accepted mechanism. Thus, myelination is not a simple means of insulation or acceleration of impulse conduction, but it is rather an exquisite way of actively regulating the timing of communication among various neuronal connections with different length

Fast activation of feedforward inhibitory neurons from thalamic input and its relevance to the regulation of spike sequences in the barrel cortex

Thalamocortical afferents innervate both excitatory and inhibitory cells, the latter in turn producing disynaptic feedforward inhibition, thus creating fast excitation–inhibition sequences in the cortical cells. Since this inhibition is disynaptic, the time lag of the excitation–inhibition sequence could be ∼2–3 ms, while it is often as short as only slightly above 1 ms; the mechanism and function of such fast IPSPs are not fully understood. Here we show that thalamic activation of inhibitory neurons precedes that of excitatory neurons, due to increased conduction velocity of thalamic axons innervating inhibitory cells. Developmentally, such latency differences were seen only after the end of the second postnatal week, prior to the completion of myelination of the thalamocortical afferent. Furthermore, destroying myelination failed to extinguish the latency difference. Instead, axons innervating inhibitory cells had consistently lower threshold, indicating they had larger diameter, which is likely to underlie the differential conduction velocity. Since faster activation of GABAergic neurons from the thalamus can not only curtail monosynaptic EPSPs but also make disynaptic ISPSs precede disynaptic EPSPs, such suppression theoretically enables a temporal separation of thalamically driven mono- and disynaptic EPSPs, resulting in spike sequences of ‘L4 leading L2/3’. By recording L4 and L2/3 cells simultaneously, we found that suppression of IPSPs could lead to deterioration of spike sequences. Thus, from the end of the second postnatal week, by activating GABAergic neurons prior to excitatory neurons from the thalamus, fast feedforward disynaptic suppression on postsynaptic cells may play a role in establishing the spike sequences of ‘L4 leading L2/3 cells’

Phase Advance of the Light-Dark Cycle Perturbs Diurnal Rhythms of Brain-derived Neurotrophic Factor and Neurotrophin-3 Protein Levels, Which Reduces Synaptophysin-positive Presynaptic Terminals in the Cortex of Juvenile Rats

In adult rat brains, brain-derived neurotrophic factor (BDNF) rhythmically oscillates according to the light-dark cycle and exhibits unique functions in particular brain regions. However, little is known of this subject in juvenile rats. Here, we examined diurnal variation in BDNF and neurotrophin-3 (NT-3) levels in 14-day-old rats. BDNF levels were high in the dark phase and low in the light phase in a majority of brain regions. In contrast, NT-3 levels demonstrated an inverse phase relationship that was limited to the cerebral neocortex, including the visual cortex, and was most prominent on postnatal day 14. An 8-h phase advance of the light-dark cycle and sleep deprivation induced an increase in BDNF levels and a decrease in NT-3 levels in the neocortex, and the former treatment reduced synaptophysin expression and the numbers of synaptophysin-positive presynaptic terminals in cortical layer IV and caused abnormal BDNF and NT-3 rhythms 1 week after treatment. A similar reduction of synaptophysin expression was observed in the cortices of Bdnf gene-deficient mice and Ca2+-dependent activator protein for secretion 2 gene-deficient mice with abnormal free-running rhythm and autistic-like phenotypes. In the latter mice, no diurnal variation in BDNF levels was observed. These results indicate that regular rhythms of BDNF and NT-3 are essential for correct cortical network formation in juvenile rodents