Biology subjects

Mallet, N. P.

Publications and source records attributed to Mallet, N. P..

4 recordsLinked to original sources

bioRxiv2026

Generation mechanisms and species-specific properties of parkinsonian beta oscillations in the basal ganglia

The basal ganglia (BG), thalamus and cortex form the BG-thalamo-cortical (BGTC) network, which is essential for voluntary movement and centrally involved in Parkinson's disease (PD). In both patients and animal models, BG neuronal activity exhibits exaggerated oscillatory synchronization in the beta frequencies (13-30 Hz). Theoretical studies have proposed multiple network mechanisms for the generation of these abnormal beta oscillations. However, key properties, such as frequency and power distribution across BG nuclei, vary substantially among patients and between animal models (rodents vs. non-human primates). This variability complicates direct comparisons between theoretical models and experimental data, and questions whether distinct neuronal mechanisms may underlie beta oscillations across species. In an experimentally constrained BGTC network model with species-specific parameters (synaptic, neuronal, and network properties), we evaluate the features of abnormal beta oscillatory activity generated by different mechanisms. The network's negative feedback loops serve as potential sources of spontaneous oscillations. Using rodent- or primate-constrained models, we compare the spectral properties of oscillatory activity across network populations for each loop and derive the expected phase relationships between populations to align predictions with existing rodent data and propose testable hypotheses for primates. We also demonstrate how oscillation frequency can be modulated when multiple generation mechanisms interact as coupled oscillators in the full network. Our results, combined with observed cross-species beta oscillations characteristics, suggest that abnormal beta oscillations likely arise from distinct mechanisms in rodents and primates.

neuroscience↗

bioRxiv2024

Beta bursts in the parkinsonian cortico-basal ganglia network form spatially discrete ensemble.

Defining spatial synchronization of pathological beta oscillations is important, given that many theories linking them to parkinsonian symptoms propose a reduction in the dimensionality of the coding space within and/or across cortico-basal ganglia structures. Such spatial synchronization could arise from a single process, with widespread entrainment of neurons to the same oscillation. Alternatively, the partially segregated structure of cortico-basal ganglia loops could provide a substrate for multiple ensembles that are independently synchronized at beta frequencies. Addressing this question requires an analytical approach that identifies groups of signals with a statistical tendency for beta synchronisation, which is unachievable using standard pairwise measures. Here, we utilized such an approach on multichannel recordings of background unit activity (BUA) in the external globus pallidus (GP) and subthalamic nucleus (STN) in parkinsonian rats. We employed an adapted version of a principle and independent component analysis-based method commonly used to define assemblies of single neurons (i.e., neurons that are synchronized over short timescales). This analysis enabled us to define whether changes in the power of beta oscillations in local ensembles of neurons (i.e., the BUA recorded from single contacts) consistently covaried over time, forming a "beta ensemble". Multiple beta ensembles were often present in single recordings and could span brain structures. Membership of a beta ensemble predicted significantly higher levels of short latency (<5ms) synchrony in the raw BUA signal and phase synchronization with cortical beta oscillations, suggesting that they comprised clusters of neurons that are functionally connected at multiple levels, despite sometimes being non-contiguous in space. Overall, these findings suggest that beta oscillations do not comprise a single synchronization process, but rather multiple independent activities that can bind both spatially contiguous and non-contiguous pools of neurons within and across structures. As previously proposed, such ensembles provide a substrate for beta oscillations to constrain the coding space of cortico-basal ganglia circuits.

neuroscience↗

bioRxiv2023

Synaptic changes in pallidostriatal circuits observed in parkinsonian model triggers abnormal beta synchrony with accurate spatio-temporal properties across the basal ganglia

Excessive oscillatory activity across basal ganglia (BG) nuclei in the {beta} frequencies (12-30Hz) is a hallmark of Parkinsons disease (PD). While the link between oscillations and symptoms remains debated, exaggerated {beta} oscillations constitute an important biomarker for therapeutic effectiveness in PD. The neuronal mechanisms of {beta}-oscillation generation however remain unknown. Many existing models rely on a central role of the subthalamic nucleus (STN) or cortical inputs to BG. Contrarily, neural recordings and optogenetic manipulations in normal and parkinsonian rats recently highlighted the central role of the external pallidum (GPe) in abnormal {beta} oscillations, while showing that the integrity of STN or motor cortex is not required. Here, we evaluate the mechanisms for the generation of abnormal {beta} oscillations in a BG network model where neuronal and synaptic time constants, connectivity, and firing rate distributions are strongly constrained by experimental data. Guided by a mean-field approach, we show in a spiking neural network that several BG sub-circuits can drive oscillations. Strong recurrent STN-GPe connections or collateral intra-GPe connections drive gamma oscillations (> 40Hz), whereas strong pallidostriatal loops drive low-{beta} (10-15Hz) oscillations. We show that pathophysiological strengthening of striatal and pallidal synapses following dopamine depletion leads to the emergence of synchronized oscillatory activity in the mid-{beta} range with spike-phase relationships between BG neuronal populations in-line with experiments. Furthermore, inhibition of GPe, contrary to STN, abolishes oscillations. Our modeling study uncovers the neural mechanisms underlying PD {beta} oscillations and may thereby guide the future development of therapeutic strategies. Significance statementIn Parkinsons disease, neural activity in subcortical nuclei called the basal ganglia displays abnormal oscillatory synchronization that constitutes an important biomarker for therapeutic effectiveness. The neural mechanisms for the generation of these oscillations remain unknown. Here, in a theoretical neuronal network model strongly constrained by anatomical and physiological data, we show that specific circuit modifications in basal ganglia connectivity during Parkinsons disease lead to the emergence of synchronized oscillatory activity in the network with properties that strongly agree with available experimental evidence. This and future theoretical investigations of the neural mechanisms underlying abnormal neuronal activity in Parkinsons disease are necessary to guide the future development of therapeutic strategies to ameliorate symptoms.

neuroscience↗

bioRxiv2020

A disynaptic circuit in the globus pallidus controls locomotion inhibition

Basal ganglia (BG) inhibit movement through two independent pathways, the indirect- and the hyperdirect-pathways. The globus pallidus (GP) has always been viewed as a simple relay within these two pathways, but its importance has changed drastically with the discovery of two functionally-distinct cell types, namely the prototypic and the arkypallidal neurons. Classic BG models suggest that all GP neurons receive GABAergic inputs from striato-pallidal indirect spiny projection neurons and glutamatergic inputs from subthalamic neurons. However, whether this synaptic connectivity scheme applies to both GP cell-types is currently unknown. Here, we optogenetically dissect the input organization of prototypic and arkypallidal neurons and further define the circuit mechanism underlying action inhibition in BG. Our results highlight that an increased activity of arkypallidal neurons is required to inhibit locomotion. Finally, this work supports the view that arkypallidal neurons are part of a novel disynaptic feedback loop that broadcast inhibitory control on movement execution.

neuroscience↗