In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess axon collaterals within the globus pallidus (GPe) (bridging collaterals), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches in mice to dissect the roles of dSPN GPe collaterals in motor function. We find that dSPNs projecting to the SNr send synchronous motor-related information to the GPe via axon collaterals. Inhibition of native activity in dSPN GPe terminals impairs motor activity and function via regulation of Npas1 neurons. We propose a model by which dSPN GPe axon collaterals (striatopallidal Go pathway) act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 neurons.
Axons , Neurons , Mice , Animals , Neurons/metabolism , Axons/metabolism , Globus Pallidus/physiology , Corpus Striatum/metabolism , Basal Ganglia/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism
In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess "bridging" collaterals within the globus pallidus (GPe), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches to dissect the roles of bridging collaterals in motor function. We find that dSPNs projecting to the SNr send synchronous motor-related information to the GPe via axon collaterals. Inhibition of native activity in dSPN GPe terminals impairs motor activity and function via regulation of pallidostriatal Npas1 neurons. We propose a model by which dSPN GPe collaterals ("striatopallidal Go pathway") act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 signals going back to the striatum.
Understanding how molecular geometry affects the electronic properties of single-molecule junctions experimentally has been challenging. Typically, metal-molecule-metal junctions are measured using a break-junction method where electrode separation is mechanically evolving during measurement. Here, to probe the impact of the junction geometry on conductance, we apply a sinusoidal modulation to the molecular junction electrode position. Simultaneously, we probe the nonlinearity of the current-voltage characteristics of each junction through a modulation in the applied bias at a different frequency. In turn, we show that junctions formed with molecules that have different molecule-electrode interfaces exhibit statistically distinguishable Fourier-transformed conductances. In particular, we find a marked bias dependence for the modulation of junctions where transmission is mediated thorough the van der Waals (vdW) interaction. We attribute our findings to voltage-modulated vdW interactions at the single-molecule level.
Cholinergic interneurons (CINs) in the striatum respond to salient stimuli with a multiphasic response, including a pause, in neuronal activity. Slice-physiology experiments have shown the importance of dopamine D2 receptors (D2Rs) in regulating CIN pausing, yet the behavioral significance of the CIN pause and its regulation by dopamine in vivo is still unclear. Here, we show that D2R upregulation in CINs of the nucleus accumbens (NAc) lengthens the pause in CIN activity ex vivo and enlarges a stimulus-evoked decrease in acetylcholine (ACh) levels during behavior. This enhanced dip in ACh levels is associated with a selective deficit in the learning to inhibit responding in a Go/No-Go task. Our data demonstrate, therefore, the importance of CIN D2Rs in modulating the CIN response induced by salient stimuli and point to a role of this response in inhibitory learning. This work has important implications for brain disorders with altered striatal dopamine and ACh function, including schizophrenia and attention-deficit hyperactivity disorder (ADHD).
Dopamine , Receptors, Dopamine D2 , Acetylcholine , Cholinergic Agents , Corpus Striatum , Interneurons/physiology , Nucleus Accumbens
To rival the performance of modern integrated circuits, single-molecule devices must be designed to exhibit extremely nonlinear current-voltage (I-V) characteristics1-4. A common approach is to design molecular backbones where destructive quantum interference (QI) between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) produces a nonlinear energy-dependent tunnelling probability near the electrode Fermi energy (EF)5-8. However, tuning such systems is not straightforward, as aligning the frontier orbitals to EF is hard to control9. Here, we instead create a molecular system where constructive QI between the HOMO and LUMO is suppressed and destructive QI between the HOMO and strongly coupled occupied orbitals of opposite phase is enhanced. We use a series of fluorene oligomers containing a central benzothiadiazole10 unit to demonstrate that this strategy can be used to create highly nonlinear single-molecule circuits. Notably, we are able to reproducibly modulate the conductance of a 6-nm molecule by a factor of more than 104.
Electron transport across a molecular junction is characterized by an energy-dependent transmission function. The transmission function accounts for electrons tunneling through multiple molecular orbitals (MOs) with different phases, which gives rise to quantum interference (QI) effects. Because the transmission function comprises both interfering and noninterfering effects, individual interferences between MOs cannot be deduced from the transmission function directly. Herein, we demonstrate how the transmission function can be deconstructed into its constituent interfering and noninterfering contributions for any model molecular junction. These contributions are arranged in a matrix and displayed pictorially as a QI map, which allows one to easily identify individual QI effects. Importantly, we show that exponential conductance decay with increasing oligomer length is primarily due to an increase in destructive QI. With an ability to "see" QI effects using the QI map, we find that QI is vital to all molecular-scale electron transport.
The title compound, [Mo(C5H5)(C2H3O)(C12H9O3P)(CO)2], was prepared by reaction of [Mo(C5H5)(CO)3(CH3)] with tris-(furan-2-yl)phosphane. The Mo(II) atom exhibits a four-legged piano-stool coordination geometry with the acetyl and phosphine ligands trans to each other. The O atom of the acetyl ligand points down, away from the Cp ring. In the crystal, mol-ecules form centrosymmetrical dimers via π-π inter-actions between furyl rings [the centroid-centroid distance is 3.396â (4)â Å]. The dimers are linked by C-Hâ¯O hydrogen bonds into layers parallel to (100).
