Subtypes of Midbrain Dopamine Neurons

Subramaniam, Mahalakshmi; Roeper, Jochen

doi:10.1016/b978-0-12-802206-1.00016-7

Cited by 4 publications

(3 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Future studies will address the molecular mechanisms of glucose sensing in SN DA neurons. Our first experiments indicate a complex mechanism that is not simply explained by activation of K-ATP channels or A-type K + channels, as described for pathophysiological reduction of SN DA activity in response to PD stressors (Liss et al, 1999(Liss et al, , 2005Subramaniam et al, 2014;Dragicevic et al, 2015;Subramaniam and Roeper, 2017). Dissecting these mechanism is particularly relevant in view of the high vulnerability of SN DA neurons in PD, and the emerging link between pancreatic beta cells and SN DA neurons, as well as between type II diabetes (T2DM) and PD (Eberhard, 2013;Hassan et al, 2020;Sportelli et al, 2020).…”

Section: Sn Da Neurons Are Glucose Sensors (Ge-neurons)mentioning

confidence: 72%

Multi-Electrode Array Analysis Identifies Complex Dopamine Responses and Glucose Sensing Properties of Substantia Nigra Neurons in Mouse Brain Slices

Mannal

Kleiner

Fauler

et al. 2021

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

Dopaminergic (DA) midbrain neurons within the substantia nigra (SN) display an autonomous pacemaker activity that is crucial for dopamine release and voluntary movement control. Their progressive degeneration is a hallmark of Parkinson's disease. Their metabolically demanding activity-mode affects Ca2+ homeostasis, elevates metabolic stress, and renders SN DA neurons particularly vulnerable to degenerative stressors. Accordingly, their activity is regulated by complex mechanisms, notably by dopamine itself, via inhibitory D2-autoreceptors and the neuroprotective neuronal Ca2+ sensor NCS-1. Analyzing regulation of SN DA neuron activity-pattern is complicated by their high vulnerability. We studied this activity and its control by dopamine, NCS-1, and glucose with extracellular multi-electrode array (MEA) recordings from midbrain slices of juvenile and adult mice. Our tailored MEA- and spike sorting-protocols allowed high throughput and long recording times. According to individual dopamine-responses, we identified two distinct SN cell-types, in similar frequency: dopamine-inhibited and dopamine-excited neurons. Dopamine-excited neurons were either silent in the absence of dopamine, or they displayed pacemaker-activities, similar to that of dopamine-inhibited neurons. Inhibition of pacemaker-activity by dopamine is typical for SN DA neurons, and it can undergo prominent desensitization. We show for adult mice, that the number of SN DA neurons with desensitized dopamine-inhibition was increased (~60–100%) by a knockout of NCS-1, or by prevention of NCS-1 binding to D2-autoreceptors, while time-course and degrees of desensitization were not altered. The number of neurons with desensitized D2-responses was also higher (~65%) at high glucose-levels (25 mM), compared to lower glucose (2.5 mM), while again desensitization-kinetics were unaltered. However, spontaneous firing-rates were significantly higher at high glucose-levels (~20%). Moreover, transient glucose-deprivation (1 mM) induced a fast and fully-reversible pacemaker frequency reduction. To directly address and quantify glucose-sensing properties of SN DA neurons, we continuously monitored their electrical activity, while altering extracellular glucose concentrations stepwise from 0.5 mM up to 25 mM. SN DA neurons were excited by glucose, with EC50 values ranging from 0.35 to 2.3 mM. In conclusion, we identified a novel, common subtype of dopamine-excited SN neurons, and a complex, joint regulation of dopamine-inhibited neurons by dopamine and glucose, within the range of physiological brain glucose-levels.

show abstract

Section: Sn Da Neurons Are Glucose Sensors (Ge-neurons)mentioning

confidence: 72%

Multi-Electrode Array Analysis Identifies Complex Dopamine Responses and Glucose Sensing Properties of Substantia Nigra Neurons in Mouse Brain Slices

Mannal

Kleiner

Fauler

et al. 2021

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

show abstract

“…These cortical areas in turn are innervated by a variety of thalamic nuclei [ 19 , 20 ]. The caudate also receives prominent dopaminergic input from the substantia nigra pars compacta (SNc) that provides both movement and stimulus salience/ positive/negative valence-related information [ 21 ]. By contrast, the sensorimotor loop motor and primary sensory cortical areas (excluding the olfactory cortex) send projections into the putamen/dorsolateral striatum (DLS), where there is also converging thalamic input [ 18 ].…”

Section: The Ctbg Circuitrymentioning

confidence: 99%

A Circuit-Based Information Approach to Substance Abuse Research

Lovinger

Gremel

2021

Trends in Neurosciences

View full text Add to dashboard Cite

Recent animal research on substance-use disorders (SUDs) has emphasized learning models and the identification of ‘addiction-prone’ animals. Meanwhile, basic neuroscientific research has elucidated molecular, cellular, and circuit functions with increasing sophistication. However, SUD-related research is hampered by continued arguments over which animal models are more ‘addiction like’, as well as the facile assignment of behaviors to a given brain region and vice versa. We argue that SUD-related research would benefit from a ‘bottom-up’ approach including: (i) the characterization of different brain circuits to understand their normal function as well as how they respond to drugs and contribute to SUDs; and (ii) a focus on the use patterns and neurobiological effects of different substances to understand the range of critical SUD-related in vivo phenotypes.

show abstract

“…The defining feature of a dopaminergic neuron is an ability to synthesize DA and release it both locally and at distal axon terminals (Subramaniam and Roeper, 2017; Sulzer et al, 2017). DA is synthesized by tyrosine hydroxylase and aromatic L-amino acid decarboxylase in neuronal cytosol, and packaged into synaptic and dense core vesicles via the vesicular monoamine transporter (VMAT) (Anden, 1967; Carlsson et al, 1958; Scherman et al, 1988).…”

Section: Midbrain-forebrain Da Circuitsmentioning

confidence: 99%

Endocannabinoid modulation of dopamine neurotransmission

et al. 2017

View full text Add to dashboard Cite

Dopamine (DA) is a major catecholamine neurotransmitter in the mammalian brain that controls neural circuits involved in the cognitive, emotional, and motor aspects of goal-directed behavior. Accordingly, perturbations in DA neurotransmission play a central role in several neuropsychiatric disorders. Somewhat surprisingly given its prominent role in numerous behaviors, DA is released by a relatively small number of densely packed neurons originating in the midbrain. The dopaminergic midbrain innervates numerous brain regions where extracellular DA release and receptor binding promote short- and long-term changes in postsynaptic neuron function. Striatal forebrain nuclei receive the greatest proportion of DA projections and are a predominant hub at which DA influences behavior. A number of excitatory, inhibitory, and modulatory inputs orchestrate DA neurotransmission by controlling DA cell body firing patterns, terminal release, and effects on postsynaptic sites in the striatum. The endocannabinoid (eCB) system serves as an important filter of afferent input that acts locally at midbrain and terminal regions to shape how incoming information is conveyed onto DA neurons and to output targets. In this review, we aim to highlight existing knowledge regarding how eCB signaling controls DA neuron function through modifications in synaptic strength at midbrain and striatal sites, and to raise outstanding questions on this topic.

show abstract

Subtypes of Midbrain Dopamine Neurons

Cited by 4 publications

References 152 publications

Multi-Electrode Array Analysis Identifies Complex Dopamine Responses and Glucose Sensing Properties of Substantia Nigra Neurons in Mouse Brain Slices

Multi-Electrode Array Analysis Identifies Complex Dopamine Responses and Glucose Sensing Properties of Substantia Nigra Neurons in Mouse Brain Slices

A Circuit-Based Information Approach to Substance Abuse Research

Endocannabinoid modulation of dopamine neurotransmission

Contact Info

Product

Resources

About