Lighting up pre-synaptic potentiation: An Editorial for "SynaptoPAC, an optogenetic tool for induction of presynaptic plasticity" on page 324.

This is an Editorial Highlight of a manuscript by Oldani et al. (2020) (Oldani et al. 2020) in the current issue of the Journal of Neurochemistry, in which the authors describe synaptoPAC, a new optogenetic tool. SynaptoPAC is targeted to pre-synaptic compartments and can be used for light-induced increase of the levels of cAMP. Pre-synaptic plasticity, defined as activity-dependent modulation of neurotransmitter release, occurs over a variety of time scales. At a subset of synapses in the brain, long-term forms of pre-synaptic facilitation depend on an increase in the levels of cAMP. Light-induced modulation of cAMP at synapses expressing cAMP-dependent facilitation, has the great potential to mimic pre-synaptic plasticity at genetically targeted synapses. Therefore, synaptoPAC constitutes a powerful tool to study the role of pre-synaptic potentiation in the activity of selected neuronal circuits in relation to behaving animals with a high temporal and spatial precision.

Theta Oscillations Coincide with Sustained Hyperpolarization in CA3 Pyramidal Cells, Underlying Decreased Firing.

Brain states modulate the membrane potential dynamics of neurons, influencing the functional repertoire of the network. Pyramidal cells (PCs) in the hippocampal CA3 are necessary for rapid memory encoding, which preferentially occurs during exploratory behavior in the high-arousal theta state. However, the relationship between the membrane potential dynamics of CA3 PCs and theta has not been explored. Here we characterize the changes in the membrane potential of PCs in relation to theta using electrophysiological recordings in awake mice. During theta, most PCs behave in a stereotypical manner, consistently hyperpolarizing time-locked to the duration of theta. Additionally, PCs display lower membrane potential variance and a reduced firing rate. In contrast, during large irregular activity, PCs show heterogeneous changes in membrane potential. This suggests coordinated hyperpolarization of PCs during theta, possibly caused by increased inhibition. This could lead to a higher signal-to-noise ratio in the small population of PCs active during theta, as observed in ensemble recordings.

Dynamics of cortical dendritic membrane potential and spikes in freely behaving rats.

Neural activity in vivo is primarily measured using extracellular somatic spikes, which provide limited information about neural computation. Hence, it is necessary to record from neuronal dendrites, which can generate dendritic action potentials (DAPs) in vitro, which can profoundly influence neural computation and plasticity. We measured neocortical sub- and suprathreshold dendritic membrane potential (DMP) from putative distal-most dendrites using tetrodes in freely behaving rats over multiple days with a high degree of stability and submillisecond temporal resolution. DAP firing rates were several-fold larger than somatic rates. DAP rates were also modulated by subthreshold DMP fluctuations, which were far larger than DAP amplitude, indicating hybrid, analog-digital coding in the dendrites. Parietal DAP and DMP exhibited egocentric spatial maps comparable to pyramidal neurons. These results have important implications for neural coding and plasticity.