Voltage Imaging of Cortical Oscillations in Layer 1 with Two-Photon Microscopy.

Membrane voltage oscillations in layer 1 (L1) of primary sensory cortices might be important indicators of cortical gain control, attentional focusing, and signal integration. However, electric field recordings are hampered by the low seal resistance of electrodes close to the brain surface. To study L1 membrane voltage oscillations, we synthesized a new voltage-sensitive dye, di1-ANNINE (anellated hemicyanine)-6plus, that can diffuse into tissue. We applied it with a new surgery, leaving the dura intact but allowing injection of large quantities of staining solution, and imaged cortical membrane potential oscillations with two-photon microscopy depth-resolved (25-100 µm below dura) in anesthetized and awake mice. We found delta (0.5-4 Hz), theta (4-10 Hz), low beta (10-20 Hz), and low gamma (30-40 Hz) oscillations. All oscillations were stronger in awake animals. While the power of delta, theta, and low beta oscillations increased with depth, the power of low gamma was more constant throughout L1. These findings identify L1 as an important coordination hub for the dynamic binding process of neurons mediated by oscillations.

Association with reward negatively modulates short latency phasic conditioned responses of dorsal raphe nucleus neurons in freely moving rats.

The dorsal raphe nucleus (DRN) is implicated in mood regulation, control of impulsive behavior, and in processing aversive and reward-related signals. DRN neurons show phasic responses to sensory stimuli, but whether association with reward modulates these responses is unknown. We recorded DRN neurons from rats in a contextual conditioned approach paradigm in which an auditory cue was either followed or not followed by reward, depending on a global context signal. Conditioned approach (licking) occurred after cues in the reward context, but was suppressed in the no-reward context. Many DRN neurons showed short-latency phasic activations in response to the cues. There was striking contextual bias, with more and stronger excitations in the no-reward context than in the reward context. Therefore, DRN activity scaled inversely with cue salience and with the probability of subsequent conditioned approach. Tonic changes were similarly discriminatory, with increases being dominant after cues in the no-reward context, when licking was suppressed, and tonic decreases in rate dominant after reward-predictive cues during expression of conditioned licking. Phasic and tonic DRN responses thus provide signals of consistent valence but over different timescales. The tonic changes in activity are consistent with previous data and hypotheses relating DRN activity to response suppression and impulse control. Phasic responses could contribute to this via online modulation of attention allocation through projections to sensory-processing regions.