Thalamus orchestrates local acetylcholine-dependent dopamine release in the learning striatum.
Dopamine is essential for striatal function and learning. Striatal dopamine release can be triggered by dopamine cell firing, but also by coordinated cholinergic interneuron activity, which stimulates dopamine release via presynaptic nicotinic acetylcholine receptors on dopamine axons. While acetylcholine-dependent dopamine release is well-documented ex vivo and under artificial optogenetic stimulation in vivo, its role during natural behavior has remained unclear. One possible endogenous driver of acetylcholine-dependent dopamine release is thalamic input, which provides strong excitatory drive to cholinergic interneurons. To examine whether thalamic input provokes acetylcholine-dependent dopamine release during behavior, we performed simultaneous fiber photometry recordings of striatal dopamine (GRAB-rDA3m) and thalamic axon activity (gCaMP8m) in the dorsomedial (DMS) and dorsolateral striatum (DLS) of mice learning the accelerating rotarod, a striatal-dependent task that demands precise and effortful motor control. Recordings were obtained on- and off-task and across days of training to capture the full arc of learning. Dopamine transients in DMS, but not DLS, were frequently coupled to peaks in thalamic axon activity via an acetylcholine-dependent mechanism. The occurrence of these thalamic-evoked DMS dopamine transients depended on learning, task engagement, and the recent history of dopamine activity, but did not contribute to motor error signals. Together, these findings establish thalamic input as a physiological driver of acetylcholine-dependent dopamine release in DMS. Moreover, they reveal that striatal sensitivity to this local release mechanism is dynamically gated by dopaminergic history, providing a compelling framework for understanding how local and soma-triggered dopamine signals are coordinated to support learning.
Neuropixels Opto: combining high-resolution electrophysiology and optogenetics.
High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 70-μm-wide, 1-cm-long shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In the mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent a promising tool for recording, identifying and manipulating neuronal populations.
Dual neuromodulatory dynamics underlie birdsong learning.
Although learning in response to extrinsic reinforcement is theorized to be driven by dopamine signals that encode the difference between expected and experienced rewards, skills that enable verbal or musical expression can be learned without extrinsic reinforcement. Instead, spontaneous execution of these skills is thought to be intrinsically reinforcing. Whether dopamine signals similarly guide learning of these intrinsically reinforced behaviours is unknown. In juvenile zebra finches learning from an adult tutor, dopamine signalling in a song-specialized basal ganglia region is required for successful song copying, a spontaneous, intrinsically reinforced process. Here we show that dopamine dynamics in the song basal ganglia faithfully track the learned quality of juvenile song performance on a rendition-by-rendition basis. Furthermore, dopamine release in the basal ganglia is driven not only by inputs from midbrain dopamine neurons classically associated with reinforcement learning but also by song premotor inputs, which act by means of local cholinergic signalling to elevate dopamine during singing. Although both cholinergic and dopaminergic signalling are necessary for juvenile song learning, only dopamine tracks the learned quality of song performance. Therefore, dopamine dynamics in the basal ganglia encode performance quality during self-directed, long-term learning of natural behaviours.
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Most Popular Recent Articles
Quantum dynamics of photoexcited charge transfer in bridge-mediated porphyrin-naphthalenetetracarboxylic dianhydride donor-acceptor system.
Photoinduced charge transfer (CT) in donor-bridge-acceptor (D-B-A) systems is governed by the interplay between electronic coupling and vibronic interactions. Here, we investigated ultrafast CT dynamics in Zn-porphyrin-NTCDA complexes connected through either an extended 1,4-diethynylphenylene (DEP) bridge or an ethynyl linker. The excited-state dynamics are described using a linear vibronic coupling Hamiltonian combined with quantum dynamical wavepacket propagation, thereby allowing explicit treatment of multidimensional nuclear motions. Electronic-structure analysis shows that the conjugated DEP bridge provides stronger donor-acceptor communication and more favorable energetic alignment between locally excited and CT states. As a result, population transfer to the CT configuration occurs on an ultrafast timescale of ∼9 fs. In contrast, modifying the bridge reduces π-conjugation and electronic interaction, leading to slower CT dynamics of ∼25 fs. Systematic inclusion of increasing numbers of vibrational modes reveals that cooperative multimode coupling enhances vibronic dephasing, stabilizes the charge-separated population, and suppresses coherent recurrences in the electronic dynamics. The simulations, therefore, identify bridge-mediated conjugation and multidimensional vibronic interactions as key factors governing charge-separation efficiency in these architectures. These findings provide molecular-level insights into how bridge structure and vibrational motions cooperatively regulate CT dynamics in D-B-A systems.
Dissipative quantum geometric phase in the spin-boson system.
We explore how the dissipative geometric phase evolves within the spin-boson model, focusing specifically on coupling to an Ohmic bath in the weakly coherent regime. To determine the non-unitary time evolution of the system's reduced density matrix, we employ the non-interacting blip approximation (NIBA). For the localized pure initial state used throughout, we derive a compact Bloch-sphere expression showing that the mixed-state geometric phase is a weighted azimuthal winding of the dissipative trajectory. We then map geometric-phase accumulation across various system-bath coupling strengths, temperatures, static biases, and bath cutoff frequencies. Benchmarking representative results against the numerically exact time-evolving matrix product operator (TEMPO) technique shows that NIBA reproduces the population dynamics almost indistinguishably. It also captures the geometric phase quantitatively and qualitatively, although TEMPO reveals a clearer trend in the stationary coherence. Our results show that quantum dissipation suppresses the geometric phase through two complementary mechanisms: thermal noise reduces the state's purity, while static bias localizes the dynamics and reduces the accessible geometric area.
Simulating closed- and open-quantum photoinduced electron dynamics for time-resolved NEXAFS.
We present a real-time method based on the propagation of the time-dependent Schrödinger equation in the space of electronic states to compute near edge x-ray absorption fine structure (NEXAFS) spectra of molecules from the ground or a valence excited state. Transition dipole moments between a core and a valence state are computed from linear-response time-dependent density functional theory implemented in the Amsterdam Modeling Suite package by using Slater-Condon rules following two distinct core and valence excited-state calculations. The implementation is compatible with any singly excited ansatz and generalizable to correlated wavefunction methods. The method has been applied to the ultrafast internal conversion observed in the gas-phase thymine, when excited to bright ππ* (S2) state. We have computed the NEXAFS O K-edge from the electronic ground state, S2, and the dark nπ* (S1) state. We have reproduced the experimental spectrum [Wolf et al., Nat. Commun. 8, 29 (2017)] after the pump, showing the peak at 526.5 eV associated with S1. The stochastic Schrödinger equation has been used to get a time-resolved NEXAFS signal, introducing the experimental S2 → S1 decay time of 60 fs. An implicit pump initializes the thymine in the S2 state, and an x-ray pulse probes the system at various delay times (and distinct thymine structures), leading to a time-resolved spectral profile that captures the S2 → S1 population transfer. Slower relaxation from S1 to the ground state has been also considered in a multiple-channel modeling of the dynamics. Ground- and excited-state NEXAFS spectra of cis and trans isomers of azobenzene have been also computed.