Cocaine regulates sensory filtering in cortical pyramidal neurons.

Exposure to cocaine leads to robust changes in the structure and function of neurons within the mesocorticolimbic pathway. However, little is known about how cocaine influences the processing of information within the sensory cortex. We address this by using patch-clamp and juxtacellular voltage recordings and two-photon Ca2+ imaging in vivo to investigate the influence of acute cocaine exposure on layer 2/3 (L2/3) pyramidal neurons within the primary somatosensory cortex (S1). Here, cocaine dampens membrane potential state transitions and decreases spontaneous somatic action potentials and Ca2+ transients. In contrast to the uniform decrease in background spontaneous activity, cocaine has a heterogeneous influence on sensory encoding, increasing tactile-evoked responses in dendrites that do not typically encode sensory information and decreasing responses in those dendrites that are more reliable sensory encoders. Combined, these findings suggest that cocaine acts as a filter that suppresses background noise to selectively modulate incoming sensory information.

Local and Global Dynamics of Dendritic Activity in the Pyramidal Neuron.

There has been increasing interest in the measurement and comparison of activity across compartments of the pyramidal neuron. Dendritic activity can occur both locally, on a single dendritic segment, or globally, involving multiple compartments of the single neuron. Little is known about how these dendritic dynamics shape and contribute to information processing and behavior. Although it has been difficult to characterize local and global activity in vivo due to the technical challenge of simultaneously recording from the entire dendritic arbor and soma, the rise of calcium imaging has driven the increased feasibility and interest of these experiments. However, the distinction between local and global activity made by calcium imaging requires careful consideration. In this review we describe local and global activity, discuss the difficulties and caveats of this distinction, and present the evidence of local and global activity in information processing and behavior.

Neural basis of anticipation and premature impulsive action in the frontal cortex.

Planning motor actions can improve behavioral performance; however, it can also lead to premature actions. Although the anterior lateral motor cortex (ALM) is known to be important for correct motor planning, it is currently unknown how it contributes to premature impulsive motor output. This was addressed using whole-cell voltage recordings from layer 2/3 pyramidal neurons within the ALM while mice performed a cued sensory association task. Here, a robust voltage response was evoked during the auditory cue, which was greater during incorrect premature behavior than during correct performance in the task. Optogenetically suppressing ALM during the cued sensory association task led to enhanced behavior, with fewer, and more delayed, premature responses and faster correct responses. Taken together, our findings extend the current known roles of the ALM, illustrating that ALM plays an important role in impulsive behavior by encoding and influencing premature motor output.

Dendritic Compartmentalization of Learning-Related Plasticity.

The dendrites of cortical pyramidal neurons receive synaptic inputs from different pathways that are organized according to their laminar target. This architectural scheme provides cortical neurons with a spatial mechanism to separate information, which may support neural flexibility required during learning. Here, we investigated layer-specific plasticity of sensory encoding following learning by recording from two different dendritic compartments, tuft and basal dendrites, of layer 2/3 (L2/3) pyramidal neurons in the auditory cortex of mice. Following auditory fear conditioning, auditory-evoked Ca2+ responses were enhanced in tuft, but not basal, dendrites leading to increased somatic action potential output. This is in direct contrast to the long held (and debated) hypothesis that, despite extensive dendritic arbors, neurons function as a simple one-compartment model. Two computational models of varying complexity based on the experimental data illustrated that this learning-related increase of auditory responses in tuft dendrites can account for the changes in somatic output. Taken together, we illustrate that neurons do not function as a single compartment, and dendritic compartmentalization of learning-related plasticity may act to increase the computational power of pyramidal neurons.