Synchronous spiking of cerebellar Purkinje cells during control of movements

The information that the brain transmits from one region to another is often viewed through the lens of firing rates. However, if the output neurons could vary the timing of their spikes with respect to each other, then through synchronization they could highlight information that may be critical for control of behavior. In the cerebellum, the computations that are performed by the cerebellar cortex are conveyed to the nuclei via inhibition. Yet, synchronous activity entrains nucleus neurons, making them fire. Does the cerebellar cortex rely on spike synchrony within populations of Purkinje cells (P-cells) to convey information to the nucleus? We recorded from multiple P-cells while marmosets performed saccadic eye movements and organized them into populations that shared a complex spike response to error. Before movement onset, P-cells transmitted information via a rate code: the simple spike firing rates predicted the direction and velocity of the impending saccade. However, during the saccade, the spikes became temporally aligned within the population, signaling when to stop the movement. Thus, the cerebellar cortex relies on spike synchronization within a population of P-cells, not individual firing rates, to convey to the nucleus when to stop a movement.

Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior

In vitro work revealed that excitatory synaptic inputs to hippocampal inhibitory interneurons could undergo Hebbian, associative, or non-associative plasticity. Both behavioral and learning-dependent reorganization of these connections has also been demonstrated by measuring spike transmission probabilities in pyramidal cell-interneuron spike cross-correlations that indicate monosynaptic connections. Here we investigated the activity-dependent modification of these connections during exploratory behavior in rats by optogenetically inhibiting pyramidal cell and interneuron subpopulations. Light application and associated firing alteration of pyramidal and interneuron populations led to lasting changes in pyramidal-interneuron connection weights as indicated by spike transmission changes. Spike transmission alterations were predicted by the light-mediated changes in the number of pre- and postsynaptic spike pairing events and by firing rate changes of interneurons but not pyramidal cells. This work demonstrates the presence of activity-dependent associative and non-associative reorganization of pyramidal-interneuron connections triggered by the optogenetic modification of the firing rate and spike synchrony of cells.

Concomitant processing of choice and outcome in frontal corticostriatal ensembles correlates with performance of rats

SummaryThe frontal cortex-basal ganglia network plays a pivotal role in adaptive goal-directed behaviors. Medial frontal cortex (MFC) encodes information about choices and outcomes into sequential activation of neural population, or neural trajectory. While MFC projects to the dorsal striatum (DS), whether DS also displays temporally coordinated activity remains unknown. We studied this question by simultaneously recording neural ensembles in the MFC and DS of rodents performing an outcome-based alternative choice task. We found that the two regions exhibited highly parallel evolution of neural trajectories, transforming choice information into outcome-related information. When the two trajectories were highly correlated, spike synchrony was task-dependently modulated in some MFC-DS neuron pairs. Our results suggest that neural trajectories concomitantly process decision-relevant information in MFC and DS with increased spike synchrony between these regions.

Spontaneous variability in gamma dynamics described by a linear harmonic oscillator driven by noise

SUMMARYCircuits of excitatory and inhibitory neurons can generate rhythmic activity in the gamma frequency-range (30-80Hz). Individual gamma-cycles show spontaneous variability in amplitude and duration. The mechanisms underlying this variability are not fully understood. We recorded local-field-potentials (LFPs) and spikes from awake macaque V1, and developed a noise-robust method to detect gamma-cycle amplitudes and durations. Amplitudes and durations showed a weak but positive correlation. This correlation, and the joint amplitude-duration distribution, is well reproduced by a dampened harmonic oscillator driven by stochastic noise. We show that this model accurately fits LFP power spectra and is equivalent to a linear PING (Pyramidal Interneuron Network Gamma) circuit. The model recapitulates two additional features of V1 gamma: (1) Amplitude-duration correlations decrease with oscillation strength; (2) Amplitudes and durations exhibit strong and weak autocorrelations, respectively, depending on oscillation strength. Finally, longer gamma-cycles are associated with stronger spike-synchrony, but lower spike-rates in both (putative) excitatory and inhibitory neurons. In sum, V1 gamma-dynamics are well described by the simplest possible model of gamma: A linear harmonic oscillator driven by noise.

Complex spike synchrony dependent modulation of rat deep cerebellar nuclear activity

The rules governing cerebellar output are not fully understood, but must involve Purkinje cell (PC) activity, as PCs are the major input to deep cerebellar nuclear (DCN) cells (which form the majority of cerebellar output). Here, the influence of PC complex spikes (CSs) was investigated by simultaneously recording DCN activity with CSs from PC arrays in anesthetized rats. Crosscorrelograms were used to identify PCs that were presynaptic to recorded DCN cells (presynaptic PCs). Such PCs were located within rostrocaudal cortical strips and displayed synchronous CS activity. CS-associated modulation of DCN activity included a short-latency post-CS inhibition and long-latency excitations before and after the CS. The amplitudes of the post-CS responses correlated with the level of synchronization among presynaptic PCs. A temporal precision of ≤10 ms was generally required for CSs to be maximally effective. The results suggest that CS synchrony is a key control parameter of cerebellar output.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).