Optogenetic modulation of long-range cortical circuits in awake nonhuman primates
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A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics
For accurate perception and motor control, an animal must distinguish between sensory experiences elicited by external stimuli and those elicited by its own actions. The diversity of behaviors and their complex influences on the senses make this distinction challenging. Here, we uncover an action–cue hub that coordinates motor commands with visual processing in the brain’s first visual relay. We show that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge center, integrating visual translational optic flow signals with motor copies from saccades, locomotion and pupil dynamics. The vLGN relays these signals to correct action-specific visual distortions and to refine perception, as shown for the superior colliculus and in a depth-estimation task. Simultaneously, brain-wide vLGN projections drive corrective actions necessary for accurate visuomotor control. Our results reveal an extended corollary discharge architecture that refines early visual transformations and coordinates actions via a distributed hub-and-spoke network to enable visual perception during action.
Theoretical analysis of low-power deep synergistic sono-optogenetic excitation of neurons by co-expressing light-sensitive and mechano-sensitive ion-channels
The present challenge in neuroscience is to non-invasively exercise low-power and high-fidelity control of neurons situated deep inside the brain. Although, two-photon optogenetic excitation can activate neurons to millimeter depth with sub-cellular specificity and millisecond temporal resolution, it can also cause heating of the targeted tissue. On the other hand, sonogenetics can non-invasively modulate the cellular activity of neurons expressed with mechano-sensitive proteins in deeper areas of the brain with less spatial selectivity. We present a theoretical analysis of a synergistic sono-optogenetic method to overcome these limitations by co-expressing a mechano-sensitive (MscL-I92L) ion-channel with a light-sensitive (CoChR/ChroME2s/ChRmine) ion-channel in hippocampal neurons. It is shown that in the presence of low-amplitude subthreshold ultrasound pulses, the two-photon excitation threshold for neural spiking reduces drastically by 73% with MscL-I92L-CoChR (0.021 mW/µm2), 66% with MscL-I92L-ChroME2s (0.029 mW/µm2), and 64% with MscL-I92L-ChRmine (0.013 mW/µm2) at 5 Hz. It allows deeper excitation of up to 1.2 cm with MscL-I92L-ChRmine combination. The method is useful to design new experiments for low-power deep excitation of neurons and multimodal neuroprosthetic devices and circuits.
Simultaneous tACS-fMRI reveals state- and frequency-specific modulation of hippocampal-cortical functional connectivity
Non-invasive indirect hippocampal-targeted stimulation is of broad scientific and clinical interest. Transcranial alternating current stimulation (tACS) is appealing because it allows oscillatory stimulation to study hippocampal theta (3–8 Hz) activity. We found that tACS administered during functional magnetic resonance imaging yielded a frequency-, mental state- and topologically-specific effect of theta stimulation (but not other frequencies) enhancing right (but not left) hippocampal-cortical connectivity during resting blocks but not during task blocks. Control analyses showed that this effect was not due to possible stimulation-induced changes in signal quality or head movement. Our findings are promising for targeted network modulations of deep brain structures for research and clinical intervention.
Compartmentalized dendritic plasticity in the mouse retrosplenial cortex links contextual memories formed close in time
Events occurring close in time are often linked in memory, and recent studies suggest that such memories are encoded by overlapping neuronal ensembles. However, the role of dendritic plasticity mechanisms in linking memories is unknown. Here we show that memory linking is dependent not only on neuronal ensemble overlap in the mouse retrosplenial cortex, but also on branch-specific dendritic allocation mechanisms. The same dendritic segments are preferentially activated by two linked (but not independent) contextual memories, and spine clusters added after each of two linked (but not independent) contextual memories are allocated to the same dendritic segments. Importantly, we show that the reactivation of dendrites activated during the first context exploration is sufficient to link two contextual memories. Our results demonstrate a critical role for localized dendritic plasticity in memory integration and reveal rules governing how linked and independent memories are allocated to dendritic compartments.
Central amygdala somatostatin neurons modulate stress-induced sleep-onset insomnia
Sleep-onset insomnia, characterized by difficulty falling asleep, is linked to increased health risks. Previous studies have shown that the central amygdala (CeA) plays a crucial role in stress regulation, with the somatostatin neurons in the CeA (CeASST+) involved in adaptive stress responses. However, the role of CeASST+ neurons in stress-induced sleep-onset insomnia remains unclear. In this study, we found that the activity of CeASST+ neurons is closely associated with stressful events using fiber photometry in mice. Acute optogenetic activation of CeASST+ neurons induced a rapid transition from non-rapid eye movement (NREM) sleep to wakefulness. Semi-chronic optogenetic and chemogenetic activation of CeASST+ neurons led to prolonged sleep-onset latency and increased wakefulness. Chemogenetic inhibition of these neurons ameliorated sleep-onset insomnia induced by stressful stimuli, but did not affect sleep-wake behavior under physiological conditions. Collectively, our results suggested that CeASST+ neurons are a key neural substrate for modulating stress-induced sleep-onset insomnia, without influencing physiological sleep. These findings highlight CeASST+ neurons as a promising target for treating stress-related sleep-onset insomnia in clinical practice.
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