Integration of Descending Command Systems for the Generation of Context-Specific Locomotor Behaviors

Kim, Linda; Sharma, Sandeep; Sharples, Simon A.; Mayr, Kyle A.; Kwok, Charlie H.T.; Whelan, Patrick J.

doi:10.3389/fnins.2017.00581

Cited by 54 publications

(43 citation statements)

References 259 publications

(335 reference statements)

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“…Major recipients of NAc core output include the ventral pallidum and substantia nigra pars reticulata (SNr) (Deniau, Menetrey, & Thierry, ; Mogenson, Swanson, & Wu, ; Zahm & Heimer, ). Pauses in SNr activity are associated with both disinhibition of brainstem motor regions (Kim et al., ) and periods of forward locomotion (Freeze, Kravitz, Hammack, Berke, & Kreitzer, ) and head movement (Schmidt, Leventhal, Mallet, Chen, & Berke, ), that is, behaviors seen as rats approach the reward compartment. It is therefore possible that approach behavior occurs when reward‐paired cues activate NAc core GABAergic neurons, which inhibit SNr activity and disinhibit brainstem motor regions to permit approach.…”

Section: Discussionmentioning

confidence: 99%

The role of the nucleus accumbens in learned approach behavior diminishes with training

Dobrovitsky

West

Horvitz

2019

Eur J of Neuroscience

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Nucleus accumbens dopamine plays a key role in reward‐directed approach. Past findings suggest that dopamine's role in the expression of learned behavior diminishes with extended training. However, little is known about the central substrates that mediate the shift to dopamine‐independent reward approach. In the present study, rats approached and inserted the head into a reward compartment in response to a cue signaling food delivery. On days 4 and 5 of 28‐trial‐per‐day sessions, D1 receptor antagonist R(+)‐7‐chloro‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (SCH23390) infused to the NAc core reduced the probability and speed of cued approach. The disruptive effect of D1 receptor blockade was specific to the nucleus accumbens core and not seen with drug infusions to nearby dopamine target regions. In rats that received drug infusions after extended training (days 10 or 11), accumbens core D1 receptor blockade produced little effect on the expression of the same behavior. These results could have been due to a continued accumbens mediation of cued approach even after the behavior had become independent of accumbens D1 receptors. However, accumbens core ionotropic glutamate receptor blockade disrupted cued approach during early but not late stages of training, similar to the effects of D1 antagonist infusions. The results suggest that with extended training, a nucleus accumbens D1‐dependent behavior becomes less dependent not only on nucleus accumbens D1 transmission but also on excitatory transmission in the nucleus accumbens. These findings fill an important gap in a growing literature on reorganization of striatal function over the course of training.

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Section: Discussionmentioning

confidence: 99%

The role of the nucleus accumbens in learned approach behavior diminishes with training

Dobrovitsky

West

Horvitz

2019

Eur J of Neuroscience

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“…Since the early description of "command neurons" by Wiersma and Ikeda (1964), there have been many reports describing the functions of command neurons (Kupfermann and Weiss, 1978;Puhl et al, 2012;Bouvier et al, 2015;Hampel et al, 2015;Kim et al, 2017). Extrinsic command neurons are a common feature of motor systems such as leech swimming (Kristan et al, 2005), insect leg movements (Berg et al, 2015), and vertebrate locomotion (Dubuc et al, 2008;McLean et al, 2008;Hägglund et al, 2010;Kimura et al, 2013;Bouvier et al, 2015;Grillner and El Manira, 2015).…”

Section: Si1 As a Command Neuronmentioning

confidence: 99%

Command or Obey? Homologous Neurons Differ in Hierarchical Position for the Generation of Homologous Behaviors

Sakurai

Katz

2019

J. Neurosci.

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In motor systems, higher-order neurons provide commands to lower-level central pattern generators (CPGs) that autonomously produce rhythmic motor patterns. Such hierarchical organization is often thought to be inherent in the anatomical position of the neurons. Here, however, we report that a neuron that is member of a CPG in one species acts as a higher-order neuron in another species. In the nudibranch mollusc, Melibe leonina, swim interneuron 1 (Si1) is in the CPG underlying swimming, firing rhythmic bursts of action potentials as part of the swim motor pattern. We found that its homolog in another nudibranch, Dendronotus iris, serves as a neuromodulatory command neuron for the CPG of a homologous swimming behavior. In Dendronotus, Si1 fired irregularly throughout the swim motor pattern. The burst and spike frequencies of Dendronotus swim CPG neurons correlated with Si1 firing frequency. Si1 activity was both necessary and sufficient for the initiation and maintenance of the swim motor pattern. Each Si1 was electrically coupled to all of the CPG neurons and made monosynaptic excitatory synapses with both Si3s. Si1 also bilaterally potentiated the excitatory synapse from Si3 to Si2. "Virtual neuromodulation" of both Si3-to-Si2 synapses using dynamic clamp combined with depolarization of both Si3s mimicked the effects of Si1 stimulation on the swim motor pattern. Thus, in Dendronotus, Si1 is a command neuron that turns on, maintains, and accelerates the motor pattern through synaptic and neuromodulatory actions, thereby differing from its homolog in Melibe in its functional position in the motor hierarchy.

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“…Descending motor control signals arise from coordinated activity in widely distributed brain nuclei, and are delivered to the spinal cord in discrete axon tracts (Esposito et al, 2014;Kim et al, 2017;Lemon, 2008;Lemon and Griffiths, 2005). To distinguish their function, a classic method is to monitor motor deficits that follow transection of specific supraspinal tracts.…”

Section: Aav2-retro As a Tool For Functional Dissection Of Supraspinamentioning

confidence: 99%

“…Descending axon tracts in the spinal cord originate from diverse nuclei throughout forebrain, midbrain, hindbrain and serve a wide range of motor, sensory, and autonomic functions (Kim et al, 2017;Liang et al, 2011). Coordinated activity in multiple tracts often converges on the same motor output.…”

Section: Introductionmentioning

confidence: 99%

Global connectivity and function of descending spinal input revealed by 3D microscopy and retrograde transduction

Wang¹,

Maunze²,

Tsoulfas

et al. 2018

Preprint

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The brain communicates with the spinal cord through numerous axon tracts that arise from discrete nuclei, transmit distinct functions, and often collateralize to facilitate the coordination of descending commands. In efforts to restore supraspinal connectivity after injury or disease, this complexity presents a major challenge to interpreting functional outcomes, while the wide distribution of supraspinal nuclei complicates the delivery of therapeutics. Here we harness retrograde viral vectors to overcome these challenges. We demonstrate highly efficient retrograde transduction by AAV2-Retro in adult female mice, and employ tissue clearing to visualize descending tracts and create a mesoscopic projectome for the spinal cord. Moreover, chemogenetic silencing of supraspinal neurons with retrograde vectors results in complete and reversible forelimb paralysis, illustrating effective modulation of supraspinal function. Retrograde efficacy persists even after spinal injury, highlighting therapeutic potential. These data provide a global view of supraspinal connectivity and illustrate the potential of retrograde vectors to parse the functional contributions of supraspinal inputs. SIGNIFICANCE STATEMENTThe complexity of descending inputs to the spinal cord presents a major challenge in efforts deliver therapeutics to widespread supraspinal systems, and to interpret their functional effects.Here we demonstrate highly effective gene delivery to diverse supraspinal nuclei using a retrograde viral approach and combine it with tissue clearing and 3D microscopy to map the descending projectome from brain to spinal cord. These data highlight newly developed retrograde viruses as therapeutic and research tools, while offering new insights into supraspinal connectivity.

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Integration of Descending Command Systems for the Generation of Context-Specific Locomotor Behaviors

Cited by 54 publications

References 259 publications

The role of the nucleus accumbens in learned approach behavior diminishes with training

The role of the nucleus accumbens in learned approach behavior diminishes with training

Command or Obey? Homologous Neurons Differ in Hierarchical Position for the Generation of Homologous Behaviors

Global connectivity and function of descending spinal input revealed by 3D microscopy and retrograde transduction

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