Multiple tooth-losses during development suppress age-dependent emergence of oscillatory neural activities in the oral somatosensory cortex.

Tooth and tooth-related organs play important roles in not only mastication, but also sensory perception in the oral region. In general, sensory neural inputs during the developmental period are required for the maturation of functions in the sensory cortex. However, whether maturations of oral somatosensory cortex (OSC) require certain levels of sensory input from oral regions has been unclear. The present study investigated the influence of multiple tooth-losses during the developmental period on age-dependent emergence of rhythmic activities of population neurons in the OSC. Low-frequency electrical stimulation was delivered to layer IV and field potentials were recorded from layer II/III in the OSC of rat brain slices. In control rats, N-methyl-d-aspartate (NMDA) receptor-dependent oscillation at 8-10 Hz appeared during postnatal weeks 2-3. In rats with extraction of multiple teeth at 17-18 days old, oscillation did not appear even at maturity, whereas in rats with multiple teeth extracted at 37-38 days old, oscillation appearances were maintained in maturity. Thus, emergence of oscillation in the OSC was suppressed by multiple tooth-losses during postnatal 2-3 weeks. These results suggest that sufficient neural inputs from the teeth and tooth-related organs during developmental periods are essential for maturation of neural functions in the OSC.

Cyclic AMP-dependent attenuation of oscillatory-activity-induced intercortical strengthening of horizontal pathways between insular and parietal cortices.

Cyclic AMP (cAMP) is a key intracellular second messenger, and the intracellular cAMP signaling pathway acts to modulate various brain functions. We have previously reported that low-frequency insular cortex stimulation in rat brain slices switches on a voltage oscillator in the parietal cortex that delivers signals horizontally back and forth under caffeine application. The oscillatory activities are N-methyl-D-aspartate (NMDA) receptor-dependent, and the role of oscillation is to strengthen functional intercortical connections. The present study investigated actions of the cAMP signaling pathway on caffeine-induced strengthening of intercortical connections and tried to confirm the role of oscillation on intercortical strengthening by focusing on the cAMP pathway. After induction of parietal oscillation by insular cortex stimulation in caffeine-containing medium, application of membrane-permeable cAMP analog, bromo-cAMP, diminished oscillatory signal delivery from the parietal cortex, but initial insulo-parietal signal propagation remained strong. When oscillatory activities were reduced with co-application of caffeine and bromo-cAMP from the beginning, initial insulo-parietal propagation was established, but amplitudes of propagating wavelets and propagating velocity were reduced. Thus, cAMP-dependent diminution of caffeine-induced NMDA-receptor-dependent oscillatory signal delivery causes attenuation of intercortical strengthening of horizontal pathways between insular and parietal cortices. This finding suggests that the intracellular cAMP signaling pathway has the ability to regulate extracellular communications at the network level, and also that full expression of strengthened intercortical signal communication requires sufficient NMDA-receptor-dependent oscillatory neural activities.

NMDA receptor-dependent oscillatory signal outputs from the retrosplenial cortex triggered by a non-NMDA receptor-dependent signal input from the visual cortex.

The retrosplenial cortex is located at a critical juncture between the visual cortex and hippocampal formation. Functions of the retrosplenial cortex at the local circuit level, however, remain unclear. Herein, we show how signals traveling from the visual cortex behave in local circuits of the retrosplenial cortex, using optical recording methods and application of caffeine to rat brain slices. Electrical signals evoked in the primary visual cortex penetrated into the deep layer of the retrosplenial granular a cortex (RSGa) and propagated further toward postsubiculum and upper layer. Non-N-methyl-D-aspartate (NMDA) receptor-dependent initial traveling signal from the visual cortex triggered NMDA receptor-dependent neural oscillation in the RSGa. Oscillatory signals originated from the local area in the deep layer of the RSGa, and the signal spread back and forth toward the visual cortex and postsubiculum, in addition to spreading toward the upper layer. From the perspective of the RSGa, extrinsic signal inputs from the visual cortex switched on neural oscillators in the RSGa that deliver NMDA receptor-dependent intrinsic signal outputs. Opening and strengthening of non-NMDA receptor-dependent input pathways from the visual cortex required NMDA receptor-dependent oscillatory neural activities. These input and output relationships indicate that the retrosplenial cortex may represent an important relay station between the visual cortex and hippocampal formation.

To-and-fro optical voltage signal propagation between the insular gustatory and parietal oral somatosensory areas in rat cortex slices.

Taste perception depends not only on special taste information processed in the insular cortex, but also on oral somesthetic processing in the parietal cortex. Many insular cortex neurons show multimodal responsiveness. Such multimodality may be enabled by signal exchange between these two cortices. By using the protocol that we have developed, a synchronized population oscillation of synaptic potentials was induced in the parietal cortex by stimulation to the insular cortex in rat neocortex slices. The spatiotemporal pattern of propagation of this oscillation was studied by recording voltage-sensitive optical signals and field potentials. The first wavelet of the oscillation was propagated from the insular stimulation site to the parietal cortex. However, the second and later wavelets propagated back from the parietal cortex to the insular cortex. The oscillation was detected in the insular cortex as well, but was actually generated in the parietal cortex. Thus, the initial peak of optical signal, sent from the insular to parietal cortex, served to generate oscillatory responses in the parietal cortex, which propagated back to the insular cortex wave-by-wave. We propose that this to-and-fro propagation may be an artificially exaggerated demonstration of an intrinsic mechanism relevant to signal exchange between the parietal and insular cortices.

Age-dependent emergence of a parieto-insular corticocortical signal flow in developing rats.

By using the procedure that we developed for inducing population oscillation, it was previously demonstrated that insular cortex stimulation can evoke insulo-parietal field potential propagation and synchronized population oscillation in the parietal cortex in slices obtained from mature rats (27-35 days old). By using the same procedure, we have now studied the reciprocal parieto-insular projection. Parietal cortex stimulation elicited synchronized population oscillation in the parietal--but not insular--cortex in mature tissues. In the insular cortex, the initial wavelet of the oscillation generated by parietal cortex stimulation propagated, but the entire oscillation did not. A prior induction--but not simultaneous occurrence--of oscillation in the parietal cortex sufficed to have this initial wavelet propagate. In immature tissue (9-10 days old), both the parietal cortex oscillation and the parieto-insular propagation were induced only with low [Mg2+]o. This age dependence is exactly the same as we previously observed for the reciprocal insulo-parietal propagation. Given that the parietal cortex receives somatosensory inputs from the oral cavity and the insular cortex receives primarily chemosensory inputs from the same source, the age-dependent changes in the availability of bidirectional signal traffic between these cortices might contribute to the development of multimodal responsiveness of taste neurons.