Orexins influence various physiological processes associated with feeding behaviour, endocrine functions and wakefulness. One component of mammalian circadian timing systems, intergeniculate leaflet (IGL) of the lateral geniculate nucleus, is thought to contribute to circadian entrainment by processing photic and non-photic/arousal-related signals. Because the IGL is possibly innervated by the orexinergic system, using in vitro extracellular recording techniques we evaluated the influence of orexin A (OXA) and orexin B (OXB) on the rate and pattern of neuronal firing in this structure. Significant increases in the activity of 33 and 28% of IGL cells were observed after locally applied OXA (1 μm) and OXB (1 μm), respectively. In the great majority of neurons responses to OXA were maintained in the presence of orexin-1 receptor OX1R antagonist, SB 334867 (10 μm). Additionally, 75% of the OXB-responsive neurons were also sensitive to an orexin-2 receptor (OX2R)-selective agonist, [Ala11, D-Leu15]-OXB (1 μm). Immunohistochemical stainings showed putative synaptic contacts between OXA- and OXB-immunoreactive fibres and neuropeptide Y, and enkephalin-positive neurons in the investigated area. The outcome of our experiments reinforces previous reports indicating the possible linkage between the orexinergic and circadian systems. To our knowledge the presented findings are the first showing the direct influence of orexins on the IGL activity, mostly through activation of OX2R.

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Key pointsr The presynaptic action potential waveform was investigated in cerebellar parallel fibres from rats.r The spike repolarization was composed of a fast tetraethylammonium-sensitive component and a slow margatoxin-sensitive depolarized after-potential (DAP). These components could be manipulated relatively independently, possibly offering independent control of synchronous and asynchronous transmitter release.r Axonal electrical activation sometimes gave bursts of action potentials at the soma; these bursts were created by the axon because they invaded the soma at membrane potentials well below the somatic spike threshold.r Axonal bursts could reliably be induced by increasing the DAP pharmacologically, suggesting that proper control of DAP amplitude is necessary to suppress axonal bursting.r The fast repolarization was particularly well controlled because blockers of three groups of K + channels (tetraethylammonium, margatoxin and quinine) were needed to abolish it.Abstract Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter. We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K + channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K + channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K + channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

We studied the ability of typical unmyelinated cortical axons to conduct action potentials at fever‐like temperatures because fever often gives CNS symptoms. We investigated such axons in cerebellar and hippocampal slices from 10 to 25 days old rats at temperatures between 30 and 43°C. By recording with two electrodes along axonal pathways, we confirmed that the axons were able to initiate action potentials, but at temperatures >39°C, the propagation of the action potentials to a more distal recording site was reduced. This temperature‐sensitive conduction may be specific for the very thin unmyelinated axons because similar recordings from myelinated CNS axons did not show conduction failures. We found that the conduction fidelity improved with 1 mmol/L TEA in the bath, probably due to block of voltage‐sensitive potassium channels responsible for the fast repolarization of action potentials. Furthermore, by recording electrically activated antidromic action potentials from the soma of cerebellar granule cells, we showed that the axons failed less if they were triggered 10–30 msec after another action potential. This was because individual action potentials were followed by a depolarizing after‐potential, of constant amplitude and shape, which facilitated conduction of the following action potentials. The temperature‐sensitive conduction failures above, but not below, normal body temperature, and the failure‐reducing effect of the spike's depolarizing after‐potential, are two intrinsic mechanisms in normal gray matter axons that may help us understand how the hyperthermic brain functions.