Comparison of Actions between L-DOPA and Different Dopamine Agonists in Striatal DA-Depleted Microcircuits In Vitro: Pre-Clinical Insights

Lara-González, Esther; Duhne, Mariana; Ávila‐Cascajares, Fatima; Cruz, Silvia L.; Bargas, José

doi:10.1016/j.neuroscience.2019.04.058

Cited by 13 publications

(52 citation statements)

References 68 publications

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“…A heterogeneous and not a conspicuous pattern of activity between PV+ neurons or between PV+ and PV− neurons was observed, despite the presence of significant coactivity peaks (Berke, 2011). (d) An adequate cortical stimulus activates the striatal microcircuit during several minutes, and the same result was obtained after bath addition of 2 µM NMDA (Lara‐Gonzalez et al, 2019). A representative raster plot where dots in each row represent the activity of a different neuron is shown.…”

Section: Resultsmentioning

confidence: 72%

“…An adequate cortical stimulus may activate the striatal microcircuit during several minutes and the same result is obtained after bath addition of 2 µM NMDA (Lara‐Gonzalez et al, 2019). PV+ neuron activity was evoked in the striatal microcircuit after cortical stimulation (schematized in Figure 2a).…”

Section: Resultsmentioning

confidence: 86%

“…Single neuron positions in the y‐axis were sorted so that those neurons active before light stimulus appeared together (left of raster plot). In this condition, very few neurons are spontaneously active (about 15 neurons in this case; Lara‐Gonzalez et al, 2019). Histogram at bottom shows correlated neuronal firing.…”

Section: Resultsmentioning

confidence: 90%

“…Because PV+ neurons may help to differentially activate or inhibit neurons in a resting microcircuit, we then asked how PV+ neurons act on already ongoing microcircuits. Raster plot in Figure 5 illustrates the optogenetic activation of PV+ neurons (arrow) in a striatal microcircuit activated by the addition of 2 µM NMDA (Carrillo‐Reid et al, 2011; Lara‐Gonzalez et al, 2019). In this case (Figure 5a), 3 PV+ neurons were initially active (green dots) from a total of 50 neurons (6%).…”

Section: Resultsmentioning

confidence: 99%

“…Previous work reported the dynamics of spontaneous activity in striatal microcircuits: While intact slices are relatively silent, DA‐depleted microcircuits show high overall activity monopolized by a dominant, highly recurrent ensemble (Carrillo‐Reid et al, 2008; Jáidar et al, 2010, 2019; Pérez‐Ortega et al, 2016). Low concentrations of NMDA or cortical stimulation in vitro produce alternating temporal sequences that go on for several minutes and transitorily release the circuit from the highly recurrent ensemble in dopamine (DA)‐depleted striatal microcircuits (Aparicio‐Juárez et al, 2019; Lara‐Gonzalez, Duhne, Ávila‐Cascajares, Cruz, & Bargas, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Activation of parvalbumin‐expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits

Duhne

Lara-González

Laville

et al. 2020

Eur J of Neuroscience

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The striatum is the largest entrance to the basal ganglia. Diverse neuron classes make up striatal microcircuit activity, consisting in the sequential activation of neuronal ensembles. How different neuron classes participate in generating ensemble sequences is unknown. In control mus musculus brain slices in vitro, providing excitatory drive generates ensemble sequences. In Parkinsonian microcircuits captured by a highly recurrent ensemble, a cortical stimulus causes a transitory reconfiguration of neuronal groups alleviating Parkinsonism. Alternation between neuronal ensembles needs interconnectivity, in part due to interneurons, preferentially innervated by incoming afferents. One main class of interneuron expresses parvalbumin (PV+ neurons) and mediates feed-forward inhibition. However, its more global actions within the microcircuit are unknown. Using calcium imaging in ex vivo brain slices simultaneously recording dozens of neurons, we aimed to observe the actions of PV+ neurons within the striatal microcircuit. PV+ neurons in active microcircuits are 5%-11% of the active neurons even if, anatomically, they are <1% of the total neuronal population. In resting microcircuits, optogenetic activation of PV+ neurons turns on circuit activity by activating or disinhibiting, more neurons than those actually inhibited, showing that feed-forward inhibition is not their only function. Optostimulation of PV+ neurons in active microcircuits inhibits and activates different neuron sets, resulting in the reconfiguration of neuronal ensembles by changing their functional connections and ensemble membership, showing that neurons may belong to different ensembles at different situations. Our results show that PV+ neurons participate in the mechanisms that generate alternation of neuronal ensembles, therefore provoking ensemble sequences.

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Section: Resultsmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activation of parvalbumin‐expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits

Duhne

Lara-González

Laville

et al. 2020

Eur J of Neuroscience

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Insulin decreases epileptiform activity in rat layer 5/6 prefrontal cortex in vitro

Villalobos

Ramírez-Sánchez

Mondragón-García

et al. 2023

Synapse

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Accumulating evidence indicates that insulin-mediated signaling in the brain may play important roles in regulating neuronal function. Alterations to insulin signaling are associated with the development of neurological disorders including Alzheimer's disease and Parkinson's disease. Also, hyperglycemia and insulin resistance have been associated with seizure activity and brain injury. In recent work, we found that insulin increased inhibitory GABA A -mediated tonic currents in the prefrontal cortex (PFC).In this work, we used local field potential recordings and calcium imaging to investigate the effect of insulin on seizure-like activity in PFC slices. Seizure-like events (SLEs) were induced by perfusing the slices with magnesium-free artificial cerebrospinal fluid (ACSF) containing the proconvulsive compound 4-aminopyridine (4-AP). We found that insulin decreased the frequency, amplitude, and duration of SLEs as well as the synchronic activity of PFC neurons evoked by 4-AP. These insulin effects were mediated by the PI3K/Akt signaling pathway and mimicked by gaboxadol (THIP), a δ GABA A receptor agonist. The effect of insulin on the number of SLEs was partially blocked by L-655,708, an inverse agonist with high selectivity for GABA A receptors containing the α5 subunit. Our results suggest that insulin reduces neuronal excitability by an increase of GABAergic tonic currents. The physiological relevance of these findings is discussed.

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Role of M₄‐receptor cholinergic signaling in direct pathway striatal projection neurons during dopamine depletion

Avilés‐Rosas,

Rendón‐Ochoa,

Hernández‐Flores

et al. 2024

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Direct pathway striatal projection neurons (dSPNs) are characterized by the expression of dopamine (DA) class 1 receptors (D1R), as well as cholinergic muscarinic M1 and M4 receptors (M1R, M4R). D1R enhances neuronal firing through phosphorylation of voltage‐gate calcium channels (CaV1 Ca2+ channels) activating Gs proteins and protein kinase A (PKA). Concurrently, PKA suppresses phosphatase PP‐1 through DARPP‐32, thus extending this facilitatory modulation. M1R also influences Ca2+ channels in SPNs through Gq proteins and protein kinase C. However, the signaling mechanisms of M4R in dSPNs are less understood. Two pathways are attributed to M4R: an inhibitory one through Gi/o proteins, and a facilitatory one via the cyclin Cdk5. Our study reveals that a previously observed facilitatory modulation via CaV1 Ca2+ channels is linked to the Cdk5 pathway in dSPNs. This result could be significant in treating parkinsonism. Therefore, we questioned whether this effect persists post DA‐depletion in experimental parkinsonism. Our findings indicate that in such conditions, M4R activation leads to a decrease in Ca2+ current and an increased M4R protein level, contrasting with the control response. Nevertheless, parkinsonian and control actions are inhibited by the Cdk5 inhibitor roscovitine, suggesting Cdk5's role in both conditions. Cdk5 may activate PP‐1 via PKA inhibition in DA depletion. Indeed, we found that inhibiting PP‐1 restores control M4R actions, implying that PP‐1 is overly active via M4Rs in DA‐depleted condition. These insights contribute to understanding how DA‐depletion alters modulatory signaling in striatal neurons. Additional working hypotheses are discussed.

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Comparison of Actions between L-DOPA and Different Dopamine Agonists in Striatal DA-Depleted Microcircuits In Vitro: Pre-Clinical Insights

Cited by 13 publications

References 68 publications

Activation of parvalbumin‐expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits

Activation of parvalbumin‐expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits

Insulin decreases epileptiform activity in rat layer 5/6 prefrontal cortex in vitro

Role of M₄‐receptor cholinergic signaling in direct pathway striatal projection neurons during dopamine depletion

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Comparison of Actions between L-DOPA and Different Dopamine Agonists in Striatal DA-Depleted Microcircuits In Vitro: Pre-Clinical Insights

Cited by 13 publications

References 68 publications

Activation of parvalbumin‐expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits

Activation of parvalbumin‐expressing neurons reconfigures neuronal ensembles in murine striatal microcircuits

Insulin decreases epileptiform activity in rat layer 5/6 prefrontal cortex in vitro

Role of M4‐receptor cholinergic signaling in direct pathway striatal projection neurons during dopamine depletion

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Role of M₄‐receptor cholinergic signaling in direct pathway striatal projection neurons during dopamine depletion