Age-Dependent Modulation of Layer V Pyramidal Neuron Excitability in the Mouse Primary Motor Cortex by D1 Receptor Agonists and Antagonists.

The primary motor cortex (M1) receives dopaminergic (DAergic) projections from the midbrain which play a key role in modulating motor and cognitive processes, such as motor skill learning. However, little is known at the level of individual neurons about how dopamine (DA) and its receptors modulate the intrinsic properties of the different neuronal subpopulations in M1 and if this modulation depends on age. Using immunohistochemistry, we first mapped the cells expressing the DA D1 receptor across the different layers in M1, and quantified the number of pyramidal neurons (PNs) expressing the D1 receptor in the different layers, in young and adult mice.

Spatiomolecular Characterization of Dopamine D2 Receptors Cells in the Mouse External Globus Pallidus.

The external globus pallidus (GPe) is part of the basal ganglia circuit and plays a key role in controlling the actions. Although, many evidence indicate that dopamine through its activation of dopamine D2 receptors (D2Rs) modulates the GPe neuronal activity, the precise spatiomolecular characterization of cell populations expressing D2Rs in the mouse GPe is still lacking. By combining single molecule in situ hybridization, cell type-specific imaging analyses, and electrophysiology slice recordings, we found that GPe D2R cells are neurons preferentially localized in the caudal portion of GPe.

Activity-dependent decline and recovery of synaptic transmission in central parts of surviving primary afferents after their peripheral cut in crayfish.

Axons deprived of their nucleus degenerate within a few days in mammals but survive for several months in crustaceans. However, it is not known whether central synapses from sensory axons may preserve their molecular machinery in the absence of spiking activity. To assess this, we used peripheral axotomy, which removes their nuclei combined with electrophysiology techniques and electron microscopy imaging.

Dopaminergic modulation of primary motor cortex: From cellular and synaptic mechanisms underlying motor learning to cognitive symptoms in Parkinson's disease.

The primary motor cortex (M1) is crucial for movement execution, especially dexterous ones, but also for cognitive functions like motor learning. The acquisition of motor skills to execute dexterous movements requires dopamine-dependent and -independent plasticity mechanisms within M1. In addition to the basal ganglia, M1 is disturbed in Parkinson's disease (PD).

Subcellular specificity of cannabinoid effects in striatonigral circuits.

Recent advances in neuroscience have positioned brain circuits as key units in controlling behavior, implying that their positive or negative modulation necessarily leads to specific behavioral outcomes. However, emerging evidence suggests that the activation or inhibition of specific brain circuits can actually produce multimodal behavioral outcomes. This study shows that activation of a receptor at different subcellular locations in the same neuronal circuit can determine distinct behaviors.

Dopamine D2-Like Receptors Modulate Intrinsic Properties and Synaptic Transmission of Parvalbumin Interneurons in the Mouse Primary Motor Cortex.

Dopamine (DA) plays a crucial role in the control of motor and higher cognitive functions such as learning, working memory, and decision making. The primary motor cortex (M1), which is essential for motor control and the acquisition of motor skills, receives dopaminergic inputs in its superficial and deep layers from the midbrain. However, the precise action of DA and DA receptor subtypes on the cortical microcircuits of M1 remains poorly understood.

D5 dopamine receptors control glutamatergic AMPA transmission between the motor cortex and subthalamic nucleus.

Corticofugal fibers target the subthalamic nucleus (STN), a component nucleus of the basal ganglia, in addition to the striatum, their main input. The cortico-subthalamic, or hyperdirect, pathway, is thought to supplement the cortico-striatal pathways in order to interrupt/change planned actions. To explore the previously unknown properties of the neurons that project to the STN, retrograde and anterograde tools were used to specifically identify them in the motor cortex and selectively stimulate their synapses in the STN.

Spinal and pontine relay pathways mediating respiratory rhythm entrainment by limb proprioceptive inputs in the neonatal rat.

The coordination of locomotion and respiration is widespread among mammals, although the underlying neural mechanisms are still only partially understood. It was previously found in neonatal rat that cyclic electrical stimulation of spinal cervical and lumbar dorsal roots (DRs) can fully entrain (1:1 coupling) spontaneous respiratory activity expressed by the isolated brainstem/spinal cord. Here, we used a variety of preparations to determine the type of spinal sensory inputs responsible for this respiratory rhythm entrainment, and to establish the extent to which limb movement-activated feedback influences the medullary respiratory networks via direct or relayed ascending pathways.

Cellular and network mechanisms of operant learning-induced compulsive behavior in Aplysia.

Background: Learning in exploratory and goal-directed behaviors can modify decision-making processes in the initiation of appropriate action and thereby transform the irregular and infrequent expression of such behaviors into inflexible, compulsive-like repetitive actions. However, the neuronal mechanisms underlying such learning-derived behavioral plasticity remain poorly understood.

Results: Appetitive operant conditioning, a form of associative learning, produces a long-lasting switch in the mollusk Aplysia's food-seeking behavior from irregular, impulsive-like radula biting movements into stereotyped, compulsive-like recurrences of this cyclic act.

Persistently active, pacemaker-like neurons in neocortex.

The neocortex is spontaneously active, however, the origin of this self-generated, patterned activity remains unknown. To detect potential "pacemaker cells," we use calcium imaging to directly identify neurons that discharge action potentials in the absence of synaptic transmissionin slices from juvenile mouse visual cortex. We characterize 60 of these neurons electrophysiologically and morphologically, finding that they belong to two classes of cells: one class composed of pyramidal neurons with a thin apical dendritic tree and a second class composed of ascending axon interneurons (Martinotti cells) located in layer 5.

State-dependent regulation of sensory-motor transmission: role of muscarinic receptors in sensory-motor integration in the crayfish walking system.

The aim of this study was to investigate a potential mechanism for state-dependent regulation of sensory-motor transmission from sensory afferents of a proprioceptor to motoneurons (MNs) in the walking system of the crayfish. This study was performed using an in vitro preparation of thoracic ganglia including motor nerves and the proprioceptor that codes movements of the second joint (coxo-basal chordotonal organ - CBCO) of the leg. Application of movements to the CBCO elicits resistance reflex responses intracellularly recorded from Dep MNs.

Large-scale imaging of cortical network activity with calcium indicators.

Bulk loading of calcium indicators has provided a unique opportunity to reconstruct the activity of cortical networks with single-cell resolution. Here we describe the detailed methods of bulk loading of AM dyes we developed and have been improving for imaging with a spinning disk confocal microscope.

Central inhibitory microcircuits controlling spike propagation into sensory terminals.

The phenomenon of afferent presynaptic inhibition has been intensively studied in the sensory neurons of the chordotonal organ from the coxobasal joint (CBCO) of the crayfish leg. This has revealed that it has a number of discrete roles in these afferents, mediated by distinct populations of interneurons. Here we examine further the effect of presynaptic inhibition on action potentials in the CBCO afferents and investigate the nature of the synapses that mediate it.

Serotonin enhances the resistance reflex of the locomotor network of the crayfish through multiple modulatory effects that act cooperatively.

Serotonin (5HT) is an endogenous amine that modifies posture in crustacea. Here, we examined the mechanisms of action of 5HT on the resistance reflex in crayfish legs. This reflex, which counteracts movements imposed on a limb, is based on a negative feedback system formed by proprioceptors that sense joint angle movements and activate opposing motoneurons.

Inhibitory component of the resistance reflex in the locomotor network of the crayfish.

The aim of this study was to investigate the inhibitory components of a resistance reflex in the walking system of the crayfish. This study was performed using an in vitro preparation of several thoracic ganglia including motor nerves and the proprioceptor that codes movements of the second joint (coxo-basipodite chordotonal organ-CBCO). Sinusoidal movements were imposed on the CBCO, and intracellular responses were recorded from levator (Lev) and depressor (Dep) motoneurons (MNs).