High and low frequency stimulation of the subthalamic nucleus induce prolonged changes in subthalamic and globus pallidus neurons

Lavian, Hagar; Ben-Porat, Hana; Korngreen, Alon

doi:10.3389/fnsys.2013.00073

Cited by 12 publications

(12 citation statements)

References 34 publications

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“…; Lavian et al . ). Today′s microdialysis methodology lacks the temporal and spatial resolution that would be required for real‐time quantification of evoked glutamate release following stimulation in specific areas of the GP.…”

Section: Discussionmentioning

confidence: 97%

“…The ability to accurately quantify the glutamate concentration evoked by selective stimulation of STN neurons can prove useful for future research in relation to maladaptive changes occurring in Parkinson's disease. Current glutamate-focused approaches implemented experimentally to increase the physiological understanding of clinically applied deep brain highfrequency stimulations in Parkinson 0 s disease mainly rely on tonic concentration changes assessed by microdialysis (Windels et al 2000;Lavian et al 2013). Today 0 s microdialysis methodology lacks the temporal and spatial resolution that would be required for real-time quantification of evoked glutamate release following stimulation in specific areas of the GP.…”

Section: Discussionmentioning

confidence: 99%

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Validated multi‐step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus

Viereckel

Konradsson-Geuken

Wallén-Mackenzie

2018

Journal of Neurochemistry

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Precise quantification of extracellular glutamate concentrations upon neuronal activation is crucial for the understanding of brain function and neurological disorders. While optogenetics is an outstanding method for the correlation between distinct neurons and their role in circuitry and behavior, the electrochemically inactive nature of glutamate has proven challenging for recording upon optogenetic stimulations. This difficulty is due to the necessity for using enzyme-coated microelectrodes and the risk for light-induced artifacts. In this study, we establish a method for the combination of in vivo optogenetic stimulation with selective measurement of glutamate concentrations using enzyme-coated multielectrode arrays and amperometry. The glutamatergic subthalamic nucleus (STN), which is the main electrode target site in deep brain stimulation treatment of advanced Parkinson's disease, has recently proven opotogenetically targetable in Pitx2-Cre-transgenic mice and was here used as model system. Upon stereotactic injection of viral Channelrhodopsin2-eYFP constructs into the STN, amperometric recordings were performed at a range of optogenetic stimulation frequencies in the globus pallidus, the main STN target area, in anesthetized mice. Accurate quantification was enabled through a multi-step analysis approach based on self-referencing microelectrodes and repetition of the experimental protocol at two holding potentials, which allowed for the identification, isolation and removal of photoelectric and photoelectrochemical artifacts. This study advances the field of in vivo glutamate detection with combined optogenetics and amperometric recordings by providing a validated analysis framework for application in a wide variety of glutamate-based approaches in neuroscience.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Validated multi‐step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus

Viereckel

Konradsson-Geuken

Wallén-Mackenzie

2018

Journal of Neurochemistry

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“…Brain slices were obtained from 15‐ to 21‐day‐old Wistar rats as previously described (Stuart et al ., ; Lavian et al ., ). Rats were killed by decapitation according to the guidelines of the Bar‐Ilan University animal welfare committee.…”

Section: Methodsmentioning

confidence: 97%

Inhibitory short‐term plasticity modulates neuronal activity in the rat entopeduncular nucleus in vitro

Lavian

Korngreen

2015

Eur J of Neuroscience

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The entopeduncular nucleus (EP) is one of the basal ganglia output nuclei integrating synaptic information from several pathways within the basal ganglia. The firing of EP neurons is modulated by two streams of inhibitory synaptic transmission, the direct pathway from the striatum and the indirect pathway from the globus pallidus. These two inhibitory pathways continuously modulate the firing of EP neurons. However, the link between these synaptic inputs to neuronal firing in the EP is unclear. To investigate this input-output transformation we performed whole-cell and perforated-patch recordings from single neurons in the entopeduncular nucleus in rat brain slices during repetitive stimulation of the striatum and the globus pallidus at frequencies within the in vivo activity range of these neurons. These recordings, supplemented by compartmental modelling, showed that GABAergic synapses from the striatum, converging on EP dendrites, display short-term facilitation and that somatic or proximal GABAergic synapses from the globus pallidus show short-term depression. Activation of striatal synapses during low presynaptic activity decreased postsynaptic firing rate by continuously increasing the inter-spike interval. Conversely, activation of pallidal synapses significantly affected postsynaptic firing during high presynaptic activity. Our data thus suggest that low-frequency striatal output may be encoded as progressive phase shifts in downstream nuclei of the basal ganglia while high-frequency pallidal output may continuously modulate EP firing.

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“…Brain slices were obtained from 15-21 day old Wistar rats as previously described (Lavian et al 2013;Stuart et al 1993). Rats were killed by rapid decapitation following the guidelines of the Bar-Ilan University animal welfare committee.…”

Section: In Vitro Slice Preparationmentioning

confidence: 99%

Short term depression shapes information transmission in a constitutively active GABAergic synapse

Lavian

Korngreen

2018

Preprint

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Short-term depression is a low pass filter of synaptic information that reduces and flattens synaptic information transfer at high presynaptic firing frequencies. This view questions the relevance of spontaneous high firing rates in some networks. In the indirect pathway of the basal ganglia, spontaneously active neurons in the globus pallidus (GP) form depressing inhibitory synapses in the basal ganglia output nuclei. Using numerical modeling and whole-cell recordings from single entopeduncular nucleus (EP) neurons in rat brain slices we investigated the contribution of the different firing rates of GP neurons to information transmission in the indirect pathway. Wholecell recordings showed significant variability in steady-state depression which decreased as stimulation frequency increased. Modeling predicted that this variability would translate into different postsynaptic noise levels during constitutive presynaptic activity. Our simulations further predicted that individual GP-EP synapses mediate gain control. However, when we consider integration of multiple inputs, the large range of GP firing rates would enable different modes of information transmission in which the magnitude and temporal features of postsynaptic modulation would change as a function of present and past firing rates of GP neurons. Finally, we predict that changes in dopamine levels can shift the action of GP neurons from rate coding to gain modulation. Our results thus demonstrate how short-term synaptic depression shapes information transmission in the basal ganglia in particular and via GABAergic synapses in general.Significant statementSynapses displaying short-term depression are low-pass filters of synaptic input. Consequently, when presynaptic firing is high, little information passes to the postsynaptic neuron. However, many neurons fire at relatively high frequencies all the time. Are their synapses constantly silenced by depression? We tested this apparent contradiction in the indirect pathway of the basal ganglia, where neurons from the globus pallidus (GP) form constitutively active depressing synapses on basal ganglia output. We hypothesized that the different rates of ongoing activity underlie different modes of action for GP neurons. We show that the synaptic and structural properties of the indirect pathway map GP baseline frequencies to different postsynaptic signals, thus demonstrating how short-term synaptic depression shapes information transmission in the basal ganglia.

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High and low frequency stimulation of the subthalamic nucleus induce prolonged changes in subthalamic and globus pallidus neurons

Cited by 12 publications

References 34 publications

Validated multi‐step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus

Validated multi‐step approach for in vivo recording and analysis of optogenetically evoked glutamate in the mouse globus pallidus

Inhibitory short‐term plasticity modulates neuronal activity in the rat entopeduncular nucleus in vitro

Short term depression shapes information transmission in a constitutively active GABAergic synapse

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