Role of fast-spiking interneurons in modulating across-trial variability and within-trial correlations in the striatum.
The striatum comprises a network characterized by a highly shared feedforward inhibition (FFI) mediated by fast-spiking interneurons (FSI), which constitute only 1% of the striatal population. We investigated the dynamical consequences of this extensively shared FFI beyond inducing synchrony in a local striatal microcircuit. Our findings reveal that increased FFI sharing enhances the across-trial variability of striatal responses, activity of medium spiny neurons (MSNs), to cortical inputs, and endows the striatal network with the capacity to modulate output correlations in a bidirectional manner. Specifically, weakly shared cortical inputs become more correlated, whereas strongly shared cortical inputs are decorrelated in the presence of FSIs. These dynamic modulatory effects on MSNs, in turn, substantially alter the spiking statistics of downstream neurons in the globus pallidus, regarding across-trial variability and burstiness.
Dopamine Depletion Impairs Bilateral Sensory Processing in the Striatum in a Pathway-Dependent Manner.
Parkinson's disease (PD) is a movement disorder caused by the loss of dopaminergic innervation, particularly to the striatum. PD patients often exhibit sensory impairments, yet the underlying network mechanisms are unknown. Here we examined how dopamine (DA) depletion affects sensory processing in the mouse striatum. We used the optopatcher for online identification of direct and indirect pathway projection neurons (MSNs) during in vivo whole-cell recordings. In control mice, MSNs encoded the laterality of sensory inputs with larger and earlier responses to contralateral than ipsilateral whisker deflection. This laterality coding was lost in DA-depleted mice due to adaptive changes in the intrinsic and synaptic properties, mainly, of direct pathway MSNs. L-DOPA treatment restored laterality coding by increasing the separation between ipsilateral and contralateral responses. Our results show that DA depletion impairs bilateral tactile acuity in a pathway-dependent manner, thus providing unexpected insights into the network mechanisms underlying sensory deficits in PD. VIDEO ABSTRACT.
Ongoing movement controls sensory integration in the dorsolateral striatum.
The dorsolateral striatum (DLS) receives excitatory inputs from both sensory and motor cortical regions. In the neocortex, sensory responses are affected by motor activity, however, it is not known whether such sensorimotor interactions occur in the striatum and how they are shaped by dopamine. To determine the impact of motor activity on striatal sensory processing, we performed in vivo whole-cell recordings in the DLS of awake mice during the presentation of tactile stimuli. Striatal medium spiny neurons (MSNs) were activated by both whisker stimulation and spontaneous whisking, however, their responses to whisker deflection during ongoing whisking were attenuated. Dopamine depletion reduced the representation of whisking in direct-pathway MSNs, but not in those of the indirect-pathway. Furthermore, dopamine depletion impaired the discrimination between ipsilateral and contralateral sensory stimulation in both direct and indirect pathway MSNs. Our results show that whisking affects sensory responses in DLS and that striatal representation of both processes is dopamine- and cell type-dependent.
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Two-photon voltage imaging with rhodopsin-based sensors.
Advances in optical techniques and two-photon (2P) sensitive genetic voltage indicators (GEVIs) enabled in-depth voltage imaging at single-spike and single-cell resolution. These results were achieved using ASAP-type sensors, while rhodopsin-based GEVIs were mainly used with one-photon (1P) illumination. Here, we demonstrate compatibility of rhodopsin-based GEVIs with 2P illumination. We rationally engineer a fully genetically encoded, rhodopsin-based GEVI, just another voltage indicating sensor (Jarvis), and demonstrate its utility under 1P and 2P illumination. We further show 2P usability of the fluorescence resonance energy transfer (FRET)-opsin GEVIs pAce and Voltron2. Comparing 2P scanless with fast 2P scanning illumination revealed that responses are resolved with both approaches, but FRET-opsin GEVIs show improved signal-to-noise ratio (SNR) with low irradiance, inherent to scanless illumination. Utilizing Jarvis and pAce, we establish high-SNR action potential detection at kilohertz imaging rates in mouse hippocampal slices, zebrafish larvae, and the cortex of awake mice, demonstrating high-contrast action potential detection under 2P illumination with rhodopsin-based GEVIs in vitro and in vivo.
Diffusion in rugged energy landscapes in the presence of spatial correlations: A surprising route to Zwanzig's mean-field prediction.
Diffusion in rugged free-energy landscapes is central to diverse problems in chemical physics, biomolecular dynamics, polymer transport, and numerous disordered systems. Zwanzig's well-known classic mean-field theory predicts that roughness reduces the diffusion coefficient by an exponential factor determined solely by the variance of the disorder. The numerical studies of Banerjee, Biswas, Seki, and Bagchi (BBSB) showed that this result fails for uncorrelated Gaussian-distributed site energies because rare but deep three-site traps dominate long-time transport. BBSB introduced Gaussian spatial correlations-originally developed in astrophysics to model turbulent density fluctuations-and demonstrated that even modest correlations suppress these pathological traps and restore Zwanzig's exponential scaling. Here, we present a unified theoretical framework clarifying (i) why Zwanzig's local averaging, which may be viewed as a Gaussian cumulant expansion, can break down, particularly due to uncorrelated disorder; (ii) how Gaussian spatial correlations reshape roughness increments, eliminate asymmetric multi-site traps, and thereby recover mean-field diffusion; and (iii) a derivation showing exactly how Gaussian spatial correlations modify roughness increments, trap statistics, and, ultimately, the diffusion constant. We also provide explicit numerical triplet examples illustrating the dramatic reduction of escape times produced by spatial correlations.
Charge transfer dynamics of the Ar+(2P3/2) + N2 reaction at very low collision energies.
The charge transfer reaction Ar+ + N2 → Ar + N2+ has been studied for collision energies of 40, 90, and 170 meV with product energy and angle-differential crossed-beam velocity map imaging. Resonant multi-photon ionization was employed to create the charged reactant Ar+ in the 2P3/2 spin-orbit ground state with high purity. At the lowest studied collision energy of 40 meV, we could observe the N2+ product in the v = 0 vibrational level with a high amount of rotational excitation. This level is strongly dynamically suppressed at higher collision energies, where excited vibrational levels become accessible. In addition, a higher fraction of backward scattering is observed at this low collision energy compared to higher collision energies. This shows that the reaction dynamics of the charge-transfer reaction undergo a profound change from direct to unusual complex-mediated charge transfer dynamics at very low collision energy.