The neocortex is particularly adept at making associations and predictions about the world. Understanding how it works is one of the major problems in neuroscience but it is highly probable that the answer depends at least in part on the architecture of the cortex itself - both in terms of the individual elements and their connectivity. Since the cortex is predominantly made up of pyramidal neurons, it is absolutely fundamental to understand synaptic integration in these neurons in the context of the network in which they are embedded. A few facts are salient in this regard. Firstly, the dendrites of pyramidal neurons are highly electrogenic. In the first part of this talk I will present recent in vitro data showing that the apical dendrite is even more complex with regard to local dendritic Na⁺, Ca²⁺ and NMDA electrogenesis than previously thought.

Very little is known about how this dendritic activity manifests in awake animals and even less about its relationship to behavior. Anatomical and physiological studies have shown that top-down inputs, vital to awake behavior, project to the upper layers of the cortex where they synapse onto the tuft dendrites of pyramidal neurons.
Furthermore, a variety of anesthetics have been shown to suppress dendritic activity, and it has been suggested that the activity of the dendrites is crucially linked to conscious, awake behavior. In the second part of the talk, I show recordings of calcium activity in layer 5 pyramidal neuron dendrites using a recently developed method we dub the ‘periscope’. These data demonstrate that calcium activity is much greater in L5 pyramidal dendrites in awake rats versus anesthetized rats and also depends on the behavior of the animal. In addition, both anatomical and imaging data suggested that a pre-motor area of cortex drives this dendritic activity. Taken together, the data suggest that top-down information activates dendritic electrogenesis in primary sensory areas of the cortex that is correlated to the conscious state of the animal.

Finally, I present a hypothesis that might explain the role of pyramidal neurons in cortical network and how this depends on both their intrinsic activity and the architecture of the cortex.