Theta and gamma rhythmic coding through two spike output modes in the hippocampus during spatial navigation.

Hippocampal CA1 neurons generate single spikes and stereotyped bursts of spikes. However, it is unclear how individual neurons dynamically switch between these output modes and whether these two spiking outputs relay distinct information. We performed extracellular recordings in spatially navigating rats and cellular voltage imaging and optogenetics in awake mice. We found that spike bursts are preferentially linked to cellular and network theta rhythms (3-12 Hz) and encode an animal's position via theta phase precession, particularly as animals are entering a place field. In contrast, single spikes exhibit additional coupling to gamma rhythms (30-100 Hz), particularly as animals leave a place field. Biophysical modeling suggests that intracellular properties alone are sufficient to explain the observed input frequency-dependent spike coding. Thus, hippocampal neurons regulate the generation of bursts and single spikes according to frequency-specific network and intracellular dynamics, suggesting that these spiking modes perform distinct computations to support spatial behavior.

Striatal cholinergic interneuron membrane voltage tracks locomotor rhythms in mice.

Rhythmic neural network activity has been broadly linked to behavior. However, it is unclear how membrane potentials of individual neurons track behavioral rhythms, even though many neurons exhibit pace-making properties in isolated brain circuits. To examine whether single-cell voltage rhythmicity is coupled to behavioral rhythms, we focused on delta-frequencies (1-4 Hz) that are known to occur at both the neural network and behavioral levels. We performed membrane voltage imaging of individual striatal neurons simultaneously with network-level local field potential recordings in mice during voluntary movement. We report sustained delta oscillations in the membrane potentials of many striatal neurons, particularly cholinergic interneurons, which organize spikes and network oscillations at beta-frequencies (20-40 Hz) associated with locomotion. Furthermore, the delta-frequency patterned cellular dynamics are coupled to animals' stepping cycles. Thus, delta-rhythmic cellular dynamics in cholinergic interneurons, known for their autonomous pace-making capabilities, play an important role in regulating network rhythmicity and movement patterning.

Dopamine depletion selectively disrupts interactions between striatal neuron subtypes and LFP oscillations.

Dopamine degeneration in Parkinson's disease (PD) dysregulates the striatal neural network and causes motor deficits. However, it is unclear how altered striatal circuits relate to dopamine-acetylcholine chemical imbalance and abnormal local field potential (LFP) oscillations observed in PD. We perform a multimodal analysis of the dorsal striatum using cell-type-specific calcium imaging and LFP recording. We reveal that dopamine depletion selectively enhances LFP beta oscillations during impaired locomotion, supporting beta oscillations as a biomarker for PD. We further demonstrate that dynamic cholinergic interneuron activity during locomotion remains unaltered, even though cholinergic tone is implicated in PD. Instead, dysfunctional striatal output arises from elevated coordination within striatal output neurons, which is accompanied by reduced locomotor encoding of parvalbumin interneurons and transient pathological LFP high-gamma oscillations. These results identify a pathological striatal circuit state following dopamine depletion where distinct striatal neuron subtypes are selectively coordinated with LFP oscillations during locomotion.