substantia nigra

Metabolic spikes: from rogue electrons to Parkinson's

Conventionally, neurons are thought to be cellular units that process synaptic inputs into synaptic spikes. However, it is well known that neurons can also spike spontaneously and display a rich repertoire of firing properties with no apparent functional relevance e.g. in in vitro cortical slice preparations. In this talk, I will propose a hypothesis according to which intrinsic excitability in neurons may be a survival mechanism to minimize toxic byproducts of the cell’s energy metabolism. In neurons, this toxicity can arise when mitochondrial ATP production stalls due to limited ADP. Under these conditions, electrons deviate from the electron transport chain to produce reactive oxygen species, disrupting many cellular processes and challenging cell survival. To mitigate this, neurons may engage in ADP-producing metabolic spikes. I will explore the validity of this hypothesis using computational models that illustrate the implications of synaptic and metabolic spiking, especially in the context of substantia nigra pars compacta dopaminergic neurons and their degeneration in Parkinson's disease.

Neurotoxicity is a major health problem in Africa: focus on Parkinson's / Parkinsonism

Parkinson's disease (PD) is the second most present neurodegenerative disease in the world after Alzheimer's. It is due to the progressive and irreversible loss of dopaminergic neurons of the substantia nigra Pars Compacta. Alpha synuclein deposits and the appearance of Lewi bodies are systematically associated with it. PD is characterized by four cardinal motor symptoms: bradykinesia / akinesia, rigidity, postural instability and tremors at rest. These symptoms appear when 80% of the dopaminergic endings disappear in the striatum. According to Braak's theory, non-motor symptoms appear much earlier and this is particularly the case with anxiety, depression, anhedonia, and sleep disturbances. In 90 to 95% of cases, the causes of the appearance of the disease remain unknown, but polluting toxic molecules are incriminated more and more. In Africa, neurodegenerative diseases of the Parkinson's type are increasingly present and a parallel seems to exist between the increase in cases and the presence of toxic and polluting products such as metals. My Web conference will focus on this aspect, i.e. present experimental arguments which reinforce the hypothesis of the incrimination of these pollutants in the incidence of Parkinson's disease and / or Parkinsonism. Among the lines of research that we have developed in my laboratory in Rabat, Morocco, I have chosen this one knowing that many of our PhD students and IBRO Alumni are working or trying to develop scientific research on neurotoxicity in correlation with pathologies of the brain.

Cell-type specific alteration of excitability in the substantia nigra pars reticulata of parkinsonian mice

Neuronal hemoglobin induces loss of dopaminergic neurons in mouse Substantia nigra, cognitive deficits and cleavage of endogenous α-synuclein

Spontaneous activity of striosomal projection neurons supports maturation of striatal inputs to substantia nigra dopaminergic neurons

Therapeutic Reactivation of Dormant Neuromelanin-laden Neurons in the Substantia Nigra pars compacta by Optogenetic Stimulation

Time-course of motor behavioural, neurodegenerative and neuroinflammatory changes after viral vector-mediated overexpression of alpha-synuclein in the mouse substantia nigra

Altered firing and dopamine release in Substantia Nigra dopaminergic neurons induced by exposure to alpha-synuclein oligomers: From patch-clamp to diamond multielectrode arrays

FENS Forum 2024

HIV-1 Tat protein induces inhibition of serotonin transporter in the midbrain and increases serotonin release dynamics in the substantia nigra of inducible Tat transgenic mice

FENS Forum 2024

Signal integration and competition in a biophysical model of the substantia nigra pars reticulata

FENS Forum 2024