Layer 6b controls brain state via apical dendrites and the higher-order thalamocortical system.

The deepest layer of the cortex (layer 6b [L6b]) contains relatively few neurons, but it is the only cortical layer responsive to the potent wake-promoting neuropeptide orexin/hypocretin. Can these few neurons significantly influence brain state? Here, we show that L6b-photoactivation causes a surprisingly robust enhancement of attention-associated high-gamma oscillations and population spiking while abolishing slow waves in sleep-deprived mice. To explain this powerful impact on brain state, we investigated L6b's synaptic output using optogenetics, electrophysiology, and monoCaTChR ex vivo. We found powerful output in the higher-order thalamus and apical dendrites of L5 pyramidal neurons, via L1a and L5a, as well as in superior colliculus and L6 interneurons. L6b subpopulations with distinct morphologies and short- and long-term plasticities project to these diverse targets. The L1a-targeting subpopulation triggered powerful NMDA-receptor-dependent spikes that elicited burst firing in L5. We conclude that orexin/hypocretin-activated cortical neurons form a multifaceted, fine-tuned circuit for the sustained control of the higher-order thalamocortical system.

Does brain activity cause consciousness? A thought experiment.

Rapid advances in neuroscience have provided remarkable breakthroughs in understanding the brain on many fronts. Although promising, the role of these advancements in solving the problem of consciousness is still unclear. Based on technologies conceivably within the grasp of modern neuroscience, we discuss a thought experiment in which neural activity, in the form of action potentials, is initially recorded from all the neurons in a participant's brain during a conscious experience and then played back into the same neurons. We consider whether this artificial replay can reconstitute a conscious experience. The possible outcomes of this experiment unravel hidden costs and pitfalls in understanding consciousness from the neurosciences' perspective and challenge the conventional wisdom that causally links action potentials and consciousness.

Dendritic action potentials and computation in human layer 2/3 cortical neurons.

The active electrical properties of dendrites shape neuronal input and output and are fundamental to brain function. However, our knowledge of active dendrites has been almost entirely acquired from studies of rodents. In this work, we investigated the dendrites of layer 2 and 3 (L2/3) pyramidal neurons of the human cerebral cortex ex vivo. In these neurons, we discovered a class of calcium-mediated dendritic action potentials (dCaAPs) whose waveform and effects on neuronal output have not been previously described. In contrast to typical all-or-none action potentials, dCaAPs were graded; their amplitudes were maximal for threshold-level stimuli but dampened for stronger stimuli. These dCaAPs enabled the dendrites of individual human neocortical pyramidal neurons to classify linearly nonseparable inputs-a computation conventionally thought to require multilayered networks.

Branching into brains.

What can artificial intelligence learn from neuroscience, and vice versa?

The time window for generation of dendritic spikes by coincidence of action potentials and EPSPs is layer specific in somatosensory cortex.

The precise timing of events in the brain has consequences for intracellular processes, synaptic plasticity, integration and network behaviour. Pyramidal neurons, the most widespread excitatory neuron of the neocortex have multiple spike initiation zones, which interact via dendritic and somatic spikes actively propagating in all directions within the dendritic tree. For these neurons, therefore, both the location and timing of synaptic inputs are critical. The time window for which the backpropagating action potential can influence dendritic spike generation has been extensively studied in layer 5 neocortical pyramidal neurons of rat somatosensory cortex. Here, we re-examine this coincidence detection window for pyramidal cell types across the rat somatosensory cortex in layers 2/3, 5 and 6. We find that the time-window for optimal interaction is widest and shifted in layer 5 pyramidal neurons relative to cells in layers 6 and 2/3. Inputs arriving at the same time and locations will therefore differentially affect spike-timing dependent processes in the different classes of pyramidal neurons.

Properties of layer 6 pyramidal neuron apical dendrites.

Layer 6 (L6) pyramidal neurons are the only neocortical pyramidal cell type whose apical dendrite terminates in layer 4 rather than layer 1. Like layer 5 pyramidal neurons, they participate in a feedback loop with the thalamus and project to other cortical areas. Despite their unique location in the cortical microcircuit, synaptic integration in dendrites of L6 neurons has never been investigated. Given that all other neocortical pyramidal neurons perform active integration of synaptic inputs via local dendritic spike generation, we were interested to establish the apical dendritic properties of L6 pyramidal neurons. We measured active and passive properties of the apical dendrites of L6 pyramidal neurons in the somatosensory region of rat cortical slices using dual patch-clamp recordings from somata and dendrites and calcium imaging. We found that L6 pyramidal neurons share many fundamental dendritic properties with other neocortical pyramidal neurons, including the generation of local dendritic spikes under the control of dendritic inhibition, voltage-dependent support of backpropagating action potentials, timing-dependent dendritic integration, distally located I(h) channels, frequency-dependent Ca(2+) spike activation, and NMDA spike electrogenesis in the distal apical dendrite. The results suggest that L6 pyramidal neurons integrate synaptic inputs in layer 4 similar to the way other neocortical pyramidal neurons integrate input to layer 1. Thus, L6 pyramidal neurons can perform a similar associational task operating on inputs arriving at the granular and subgranular layers.

Dendritic spikes in apical dendrites of neocortical layer 2/3 pyramidal neurons.

Layer 2/3 (L2/3) pyramidal neurons are the most abundant cells of the neocortex. Despite their key position in the cortical microcircuit, synaptic integration in dendrites of L2/3 neurons is far less understood than in L5 pyramidal cell dendrites, mainly because of the difficulties in obtaining electrical recordings from thin dendrites. Here we directly measured passive and active properties of the apical dendrites of L2/3 neurons in rat brain slices using dual dendritic-somatic patch-clamp recordings and calcium imaging. Unlike L5 cells, L2/3 dendrites displayed little sag in response to long current pulses, which suggests a low density of I(h) in the dendrites and soma. This was also consistent with a slight increase in input resistance with distance from the soma. Brief current injections into the apical dendrite evoked relatively short (half-width 2-4 ms) dendritic spikes that were isolated from the soma for near-threshold currents at sites beyond the middle of the apical dendrite. Regenerative dendritic potentials and large concomitant calcium transients were also elicited by trains of somatic action potentials (APs) above a critical frequency (130 Hz), which was slightly higher than in L5 neurons. Initiation of dendritic spikes was facilitated by backpropagating somatic APs and could cause an additional AP at the soma. As in L5 neurons, we found that distal dendritic calcium transients are sensitive to a long-lasting block by GABAergic inhibition. We conclude that L2/3 pyramidal neurons can generate dendritic spikes, sharing with L5 pyramidal neurons fundamental properties of dendritic excitability and control by inhibition.