scholarly journals Reduced dopamine signaling impacts pyramidal neuron excitability in mouse motor cortex

2020 ◽  
Author(s):  
Olivia K. Swanson ◽  
Rosa Semaan ◽  
Arianna Maffei
Keyword(s):  
Motor Cortex ◽  
Synaptic Transmission ◽  
Voluntary Movement ◽  
Pyramidal Neurons ◽  
Output Function ◽  
Dopamine Depletion ◽  
Input Output ◽  
Motor Circuit ◽  
Neuron Excitability ◽  
Dopamine Signaling

AbstractDopaminergic modulation is essential for the control of voluntary movement, however the role of dopamine in regulating the neural excitability of the primary motor cortex (M1) is not well understood. Here, we investigated two modes by which dopamine influences the input/output function of M1 neurons. To test the direct regulation of M1 neurons by dopamine, we performed whole-cell recordings of excitatory neurons and measured excitability before and after local, acute dopamine receptor blockade. We then determined if chronic depletion of dopaminergic input to the entire motor circuit, through a mouse model of Parkinson’s Disease, was sufficient to shift M1 neuron excitability. We show that D1 and D2 receptor (D1R, D2R) antagonism altered subthreshold and suprathreshold properties of M1 pyramidal neurons in a layer-specific fashion. The effects of D1R antagonism were primarily driven by changes to intrinsic properties, while the excitability shifts following D2R antagonism relied on synaptic transmission.In contrast, chronic depletion of dopamine to the motor circuit with 6-hydroxydopamine (6OHDA) induced layer-specific synaptic transmission-dependent shifts in M1 neuron excitability that only partially overlapped with the effects of acute D1R antagonism. These results suggest that while acute and chronic changes in dopamine modulate the input/output function of M1 neurons, the mechanisms engaged are distinct depending on the duration and location of the manipulation. Our study highlights dopamine’s broad influence on M1 excitability by demonstrating the consequences of local and global dopamine depletion on neuronal input/output function.Significance statementDopaminergic signaling is crucial for the control of voluntary movement, and loss of dopaminergic transmission in the motor circuit is thought to underlie motor symptoms in those with Parkinson’s Disease (PD). Studies in animal models of PD highlight changes in M1 activity following dopamine depletion, however the mechanisms underlying this phenomenon remain poorly understood. Here we show that diminished dopamine signaling significantly alters the excitability and input/output function of M1 pyramidal neurons. The effects differed depending on the mode and location – local versus across the motor pathway – of the dopamine manipulation. Our results demonstrate how loss of dopamine can engage complex mechanisms to alter M1 neurons activity.

scholarly journals Dopamine D2 receptors modulate intrinsic properties and synaptic transmission of parvalbumin interneurons in the mouse primary motor cortex

2019 ◽  
Author(s):  
Jérémy Cousineau ◽  
Léa Lescouzères ◽  
Anne Taupignon ◽  
Lorena Delgado-Zabalza ◽  
Emmanuel Valjent ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Synaptic Transmission ◽  
Motor Skills ◽  
Primary Motor Cortex ◽  
Pyramidal Neurons ◽  
D2 Receptors ◽  
Receptor Subtypes ◽  
Parvalbumin Interneurons ◽  
Layer V ◽  
Gabaergic Synaptic Transmission

AbstractDopamine (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. The aim of this work was to investigate how DA, through the activation of D2 receptors (D2R), modulates the cellular and synaptic activity of M1 parvalbumin-expressing interneurons (PVINs) which are crucial to regulate the spike output of pyramidal neurons (PNs). By combining immunofluorescence, ex vivo electrophysiology, pharmacology and optogenetics approaches, we show that D2R activation increases neuronal excitability of PVINs and GABAergic synaptic transmission between PVINs and PNs in layer V of M1. Our data reveal a mechanism through which cortical DA modulates M1 microcircuitry and might participate in the acquisition of motor skills.Significance StatementPrimary motor cortex (M1), which is a region essential for motor control and the acquisition of motor skills, receives dopaminergic inputs from the midbrain. However, precise action of dopamine and its receptor subtypes on specific cell types in M1 remained poorly understood. Here, we demonstrate in M1 that dopamine D2 receptors (D2R) are present in parvalbumin interneurons (PVINs) and their activation increases the excitability of the PVINs, which are crucial to regulate the spike output of pyramidal neurons (PNs). Moreover the activation of the D2R facilitates the GABAergic synaptic transmission of those PVINs on layer V PNs. These results highlight how cortical dopamine modulates the functioning of M1 microcircuit which activity is disturbed in hypo- and hyperdopaminergic states.

scholarly journals A genuine layer 4 in motor cortex with prototypical synaptic circuit connectivity

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Naoki Yamawaki ◽  
Katharine Borges ◽  
Benjamin A Suter ◽  
Kenneth D Harris ◽  
Gordon M G Shepherd
Keyword(s):  
Motor Cortex ◽  
Long Range ◽  
Pyramidal Neurons ◽  
Excitatory Input ◽  
Synaptic Connections ◽  
Input Output ◽  
Layer 4 ◽  
Traditional Assumption ◽  
Dendritic Arbors ◽  
Inputs And Outputs

The motor cortex (M1) is classically considered an agranular area, lacking a distinct layer 4 (L4). Here, we tested the idea that M1, despite lacking a cytoarchitecturally visible L4, nevertheless possesses its equivalent in the form of excitatory neurons with input–output circuits like those of the L4 neurons in sensory areas. Consistent with this idea, we found that neurons located in a thin laminar zone at the L3/5A border in the forelimb area of mouse M1 have multiple L4-like synaptic connections: excitatory input from thalamus, largely unidirectional excitatory outputs to L2/3 pyramidal neurons, and relatively weak long-range corticocortical inputs and outputs. M1-L4 neurons were electrophysiologically diverse but morphologically uniform, with pyramidal-type dendritic arbors and locally ramifying axons, including branches extending into L2/3. Our findings therefore identify pyramidal neurons in M1 with the expected prototypical circuit properties of excitatory L4 neurons, and question the traditional assumption that motor cortex lacks this layer.

scholarly journals Reduced dopamine signaling impacts pyramidal neuron excitability in mouse motor cortex

eNeuro ◽  
2021 ◽  
pp. ENEURO.0548-19.2021
Author(s):  
Olivia K. Swanson ◽  
Rosa Semaan ◽  
Arianna Maffei
Keyword(s):  
Motor Cortex ◽  
Pyramidal Neuron ◽  
Neuron Excitability ◽  
Dopamine Signaling

scholarly journals Roles of Motor Cortex Neuron Classes in Reach-Related Modulation for Hemiparkinsonian Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Min Li ◽  
Xuenan Wang ◽  
Xiaomeng Yao ◽  
Xiaojun Wang ◽  
Feiyu Chen ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Cell Loss ◽  
Motor Dysfunction ◽  
Dopamine Depletion ◽  
Motor Impairments ◽  
Cortical Oscillations ◽  
The Impact

Disruption of the function of the primary motor cortex (M1) is thought to play a critical role in motor dysfunction in Parkinson’s disease (PD). Detailed information regarding the specific aspects of M1 circuits that become abnormal is lacking. We recorded single units and local field potentials (LFPs) of M1 neurons in unilateral 6-hydroxydopamine (6-OHDA) lesion rats and control rats to assess the impact of dopamine (DA) cell loss during rest and a forelimb reaching task. Our results indicated that M1 neurons can be classified into two groups (putative pyramidal neurons and putative interneurons) and that 6-OHDA could modify the activity of different M1 subpopulations to a large extent. Reduced activation of putative pyramidal neurons during inattentive rest and reaching was observed. In addition, 6-OHDA intoxication was associated with an increase in certain LFP frequencies, especially those in the beta range (broadly defined here as any frequency between 12 and 35 Hz), which become pathologically exaggerated throughout cortico-basal ganglia circuits after dopamine depletion. Furthermore, assessment of different spike-LFP coupling parameters revealed that the putative pyramidal neurons were particularly prone to being phase-locked to ongoing cortical oscillations at 12–35 Hz during reaching. Conversely, putative interneurons were neither hypoactive nor synchronized to ongoing cortical oscillations. These data collectively demonstrate a neuron type-selective alteration in the M1 in hemiparkinsonian rats. These alterations hamper the ability of the M1 to contribute to motor conduction and are likely some of the main contributors to motor impairments in PD.

scholarly journals RTP801 regulates motor cortex synaptic transmission and learning

2021 ◽  
pp. 113755
Author(s):  
Leticia Pérez-Sisqués ◽  
Núria Martín-Flores ◽  
Mercè Masana ◽  
Júlia Solana ◽  
Arnau Llobet ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Synaptic Transmission

scholarly journals Identification of Brain Electrical Activity Related to Head Yaw Rotations

Sensors ◽  
2021 ◽  
Vol 21 (10) ◽  
pp. 3345
Author(s):  
Enrico Zero ◽  
Chiara Bersani ◽  
Roberto Sacile
Keyword(s):  
Electrical Activity ◽  
Electrical Stimulus ◽  
Head Movements ◽  
Brain Electrical Activity ◽  
Output Function ◽  
Input Output ◽  
Eeg Signals ◽  
Head Turning ◽  
Identification Technique ◽  
The Brain

Automatizing the identification of human brain stimuli during head movements could lead towards a significant step forward for human computer interaction (HCI), with important applications for severely impaired people and for robotics. In this paper, a neural network-based identification technique is presented to recognize, by EEG signals, the participant’s head yaw rotations when they are subjected to visual stimulus. The goal is to identify an input-output function between the brain electrical activity and the head movement triggered by switching on/off a light on the participant’s left/right hand side. This identification process is based on “Levenberg–Marquardt” backpropagation algorithm. The results obtained on ten participants, spanning more than two hours of experiments, show the ability of the proposed approach in identifying the brain electrical stimulus associate with head turning. A first analysis is computed to the EEG signals associated to each experiment for each participant. The accuracy of prediction is demonstrated by a significant correlation between training and test trials of the same file, which, in the best case, reaches value r = 0.98 with MSE = 0.02. In a second analysis, the input output function trained on the EEG signals of one participant is tested on the EEG signals by other participants. In this case, the low correlation coefficient values demonstrated that the classifier performances decreases when it is trained and tested on different subjects.

Dopamine Increases the Gain of the Input-Output Response of Rat Prefrontal Pyramidal Neurons

2008 ◽  
Vol 99 (6) ◽  
pp. 2985-2997 ◽  
Author(s):  
Kay Thurley ◽  
Walter Senn ◽  
Hans-Rudolf Lüscher
Keyword(s):  
Working Memory ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
D1 Receptors ◽  
Input Output ◽  
Prefrontal Cortical ◽  
Noisy Input ◽  
Relationship Of

Dopaminergic modulation of prefrontal cortical activity is known to affect cognitive functions like working memory. Little consensus on the role of dopamine modulation has been achieved, however, in part because quantities directly relating to the neuronal substrate of working memory are difficult to measure. Here we show that dopamine increases the gain of the frequency-current relationship of layer 5 pyramidal neurons in vitro in response to noisy input currents. The gain increase could be attributed to a reduction of the slow afterhyperpolarization by dopamine. Dopamine also increases neuronal excitability by shifting the input-output functions to lower inputs. The modulation of these response properties is mainly mediated by D1 receptors. Integrate-and-fire neurons were fitted to the experimentally recorded input-output functions and recurrently connected in a model network. The gain increase induced by dopamine application facilitated and stabilized persistent activity in this network. The results support the hypothesis that catecholamines increase the neuronal gain and suggest that dopamine improves working memory via gain modulation.

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