Key points Perioral tactile signals are transmitted via the infraorbital nerve (ION) to trigeminal nuclei. Each cerebellar Purkinje cell (PC) receives this signal as complex spikes (CSs) via a climbing fibre (CF) emerging from the inferior olive (IO).The anatomical pathway from trigeminal nuclei to the IO is not clearly identified.In the present study, we examined candidate anatomical pathways for perioral sensory signalling by analysing CSs recorded from PCs in male mice by single unit recording.CS generation by ION stimulation was inhibited by injection of a GABAA receptor agonist, muscimol, into the contralateral mesodiencephalic junction, which is referred to as the area parafascicularis prerubralis (PfPr). The number of CSs evoked by mechanical whisker stimulation was also decreased by contralateral PfPr inhibition.These results suggest the existence of a sensory signalling pathway to the IO via the PfPr in mice. AbstractPerioral tactile signals are transmitted via the infraorbital nerve (ION) to trigeminal nuclei. Each cerebellar Purkinje cell receives this signal as complex spikes (CSs) via a climbing fibre emerging from the inferior olive (IO). However, the anatomical pathway from the trigeminal nuclei to the IO is not clearly identified. In the present study, we recorded CSs from Purkinje cells in male mice by single unit recording, and examined the signal transduction pathway. CSs were evoked by electrical stimulation of the ipsilateral or contralateral ION with a latency of 20–70 ms. CS generation by ipsilateral ION stimulation was inhibited by injection of a GABAA receptor agonist, muscimol, into the contralateral mesodiencephalic junction, ranging from around the fasciculus retroflexus to the interstitial nucleus of Cajal, which is referred to as the area parafascicularis prerubralis (PfPr). CSs evoked by contralateral ION stimulation were also suppressed by muscimol injection into the PfPr, although the effective area was more restricted. Furthermore, CSs evoked by mechanical stimulation around the whisker region were suppressed by PfPr inhibition. We also found that the primary motor cortex plays a role to suppress this signalling pathway. These results indicate the existence of an anatomical pathway for conducting perioral sensory signals to the IO via the PfPr.

Nozaki K, Kubo R, Furukawa Y. Serotonin modulates the excitatory synaptic transmission in the dentate granule cells. J Neurophysiol 115: 2997-3007, 2016. First published March 9, 2016 doi:10.1152/jn.00064.2016.-Serotonergic fibers from the raphe nuclei project to the hippocampal formation, the activity of which is known to modulate the inhibitory interneurons in the dentate gyrus. On the other hand, serotonergic modulation of the excitatory synapses in the dentate gyrus is not well examined. In the present study, we examined the effects of 5-HT on the excitatory postsynaptic potentials (EPSPs) in the dentate granule cells evoked by the selective stimulation of the lateral perforant path (LPP), the medial perforant path (MPP), or the mossy cell fibers (MCF). 5-HT depressed the amplitude of unitary EPSPs (uEPSPs) evoked by the stimulation of LPP or MPP, whereas uEPSPs evoked by MCF stimulation were little affected. The effect was partly explained by the decrease of the resting membrane resistance following the activation of 5-HT 1A receptors, which was confirmed by computer simulations. We also found that the probability of evoking uEPSP by LPP stimulation but not MPP or MCF stimulation was reduced by 5-HT and that the paired-pulse ratio of LPP-evoked EPSP but not that of MPP-or MCF-evoked ones was increased by 5-HT. These effects were blocked by 5-HT 2 antagonist, suggesting that the transmitter release in the LPP-granule cell synapse is inhibited by the activation of 5-HT 2 receptors. The present results suggest that 5-HT can modulate the EPSPs in the dentate granule cells by at least two distinct mechanisms dentate gyrus; granule cells; EPSP; serotonin

Animals suffering from uncontrollable stress sometimes show low effort to escape stress [learned helplessness (LH)]. Changes in serotonin (5-HT) signaling are thought to underlie this behavior. Although the release of 5-HT is triggered by the action potential firing of dorsal raphe nuclei 5-HT neurons, the electrophysiological changes induced by uncontrollable stress are largely unclear. Herein, we examined electrophysiological differences among 5-HT neurons in naïve rats, LH rats and rats resistant to inescapable stress (non-LH). Five-week-old male Sprague–Dawley rats were exposed to inescapable foot shocks. After an avoidance test session, rats were classified as LH or non-LH. Activity-dependent 5-HT release induced by the administration of high potassium solution was slower in free-moving LH rats. Subthreshold electrophysiological properties of 5-HT neurons were identical among the three rat groups, but the depolarization-induced spike firing was significantly attenuated in LH rats. To clarify the underlying mechanisms, potassium (K+) channels regulating the spike firing were initially examined using naïve rats. K+ channels sensitive to 500 μM tetraethylammonium caused rapid repolarization of the action potential and the small conductance calcium-activated K+ channels (SK channels) produced afterhyperpolarization. Additionally, dendrotoxin-I (DTX-I), a blocker of Kv1.1 (encoded by Kcna1), Kv1.2 (encoded by Kcna2) and Kv1.6 (encoded by Kcna6) voltage-dependent K+ channels, weakly enhanced the spike firing frequency during depolarizing current injections without changes in individual spike waveforms in naïve rats. We found that DTX-I significantly enhanced the spike firing of 5-HT neurons in LH rats. Consequently, the difference in spike firing among the three rat groups was abolished in the presence of DTX-I. These results suggest that the upregulation of DTX-I-sensitive Kv1 channels underlies the firing attenuation of 5-HT neurons in LH rats. We also found that the antidepressant ketamine facilitated the spike firing of 5-HT neurons and abolished the firing difference between LH and non-LH by suppressing DTX-I-sensitive Kv1 channels. The DTX-I-sensitive Kv1 channel may be a potential target for developing drugs to control activity of 5-HT neurons.

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