Abstract
Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previously recorded in different layers of cortical brain slices. It has been suggested that such neurons could contribute to the generation of alternating UP and DOWN states, a pattern of activity seen during slow-wave sleep. Here, we show that in layer 6b (L6b), known from our previous studies to contain neurons highly responsive to the wake-promoting transmitter hypocretin/orexin (hcrt/orx), there is a set of neurons, endowed with distinct intrinsic properties, which displayed a strong propensity to fire spontaneously in rhythmic bursts. In response to small depolarizing steps, they responded with a delayed firing of action potentials which, upon higher depolarizing steps, invariably inactivated and were followed by a depolarized plateau potential and a depolarizing afterpotential. These cells also displayed a strong hyperpolarization-activated rectification compatible with the presence of an Ih current. Most L6b neurons with such properties were able to fire spontaneously in bursts. Their bursting activity was of intrinsic origin as it persisted not only in presence of blockers of ionotropic glutamatergic and GABAergic receptors but also in a condition of complete synaptic blockade. However, a small number of these neurons displayed a mix of intrinsic bursting and synaptically driven recurrent UP and DOWN states. Most of the bursting L6b neurons were depolarized and excited by hcrt/orx through a direct postsynaptic mechanism that led to tonic firing and eventually inactivation. Similarly, they were directly excited by noradrenaline, histamine, dopamine, and neurotensin. Finally, the intracellular injection of these cells with dye and their subsequent Neurolucida reconstruction indicated that they were spiny non-pyramidal neurons. These results lead us to suggest that the propensity for slow rhythmic bursting of this set of L6b neurons could be directly impeded by hcrt/orx and other wake-promoting transmitters.
Highlights
Neocortical neurons with a rhythmic bursting pattern of activity have been reported in many in vitro studies [1,2,3,4,5,6,7]. This kind of activity has been linked to the UP and DOWN states recorded from neocortical neurons in vivo [for reviews, see Ref. [8, 9]] as well as the slow oscillations (SO) [10,11,12], which occur during slow-wave sleep (SWS)
In the process of looking for slow spontaneous rhythmic activity in layer 6b (L6b), we found a class of cells having specific intrinsic membrane properties and a propensity for slow rhythmic burst firing
In mouse cortical brain slices, we describe, in L6b, a subset of neurons characterized by distinct intrinsic properties, a prominent propensity to discharge spontaneously in rhythmic bursts and a direct sensitivity to hcrt/orx and other transmitters of arousal
Summary
Neocortical neurons with a rhythmic bursting pattern of activity have been reported in many in vitro studies [1,2,3,4,5,6,7]. 13–15), but the discovery, in cortical layers 2–3 and 5, of cells with rhythmic activities in the absence of synaptic transmission [7, 16, 17] has led to the suggestion that some scattered “pacemaker” cells could contribute to cortical rhythmic activities in conjunction with recurrent excitatory circuits [8]. This suggestion has been recently reinforced by the demonstration that optogenetic activation of a small number of infragranular neurons in vivo can initiate slow oscillatory network activity [18]. We have previously argued [19] that this layer, through projections to superficial cortical layers [27, 28], could relay the arousing action of hcrt/orx
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