Effects of Dopaminergic Modulation on the Integrative Properties of the Ventral Striatal Medium Spiny Neuron

2007 ◽  
Vol 98 (6) ◽  
pp. 3731-3748 ◽  
Author(s):  
Jason T. Moyer ◽  
John A. Wolf ◽  
Leif H. Finkel
Keyword(s):  
Neuronal Excitability ◽  
Time Window ◽  
Classical Model ◽  
D2 Receptor ◽  
Medium Spiny Neuron ◽  
Integration Time ◽  
Whole Cell ◽  
Functional Changes ◽  
Receptor Modulation ◽  
Dopaminergic Modulation

Dopaminergic modulation produces a variety of functional changes in the principal cell of the striatum, the medium spiny neuron (MSN). Using a 189-compartment computational model of a ventral striatal MSN, we simulated whole cell D1- and D2-receptor–mediated modulation of both intrinsic (sodium, calcium, and potassium) and synaptic currents (AMPA and NMDA). Dopamine (DA) modulations in the model were based on a review of published experiments in both ventral and dorsal striatum. To objectively assess the net effects of DA modulation, we combined reported individual channel modulations into either D1- or D2-receptor modulation conditions and studied them separately. Contrary to previous suggestions, we found that D1 modulation had no effect on MSN nonlinearity and could not induce bistability. In agreement with previous suggestions, we found that dopaminergic modulation leads to changes in input filtering and neuronal excitability. Importantly, the changes in neuronal excitability agree with the classical model of basal ganglia function. We also found that DA modulation can alter the integration time window of the MSN. Interestingly, the effects of DA modulation of synaptic properties opposed the effects of DA modulation of intrinsic properties, with the synaptic modulations generally dominating the net effect. We interpret this lack of synergy to suggest that the regulation of whole cell integrative properties is not the primary functional purpose of DA. We suggest that D1 modulation might instead primarily regulate calcium influx to dendritic spines through NMDA and L-type calcium channels, by both direct and indirect mechanisms.

Dopamine D2 receptor modulation of carotid body type 1 cell intracellular calcium in developing rats

2005 ◽  
Vol 288 (5) ◽  
pp. L910-L916 ◽  
Author(s):  
J. L. Carroll ◽  
K. M. Boyle ◽  
M. J. Wasicko ◽  
L. M. Sterni
Keyword(s):  
Intracellular Calcium ◽  
Time Course ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Body Type ◽  
Similar Time ◽  
Dopamine D2 ◽  
Receptor Modulation ◽  
Dopaminergic Modulation

Carotid chemoreceptor type 1 cells release dopamine, which inhibits carotid chemoreceptor activity via dopamine D2 autoreceptors on type 1 cells. Postnatal changes in dopaminergic modulation may be involved in postnatal chemoreceptor development. The present study explores dopaminergic modulation of the intracellular calcium ([Ca2+]i) response to hypoxia in type 1 cells from 1, 3, and 11- to 16-day-old rats. Using fura-2, we studied the effects of quinpirole, a D2 receptor agonist, on type 1 cell [Ca2+]i response to 90-s hypoxia challenges (Po2 ∼1–2 mmHg). Cells were sequentially exposed to the following challenges: 1) hypoxia control, 2) hypoxia plus quinpirole, and 3) hypoxia plus quinpirole plus sulpiride (D2 receptor antagonist). In the 11- to 16-day-old group, type 1 cell [Ca2+]i increased ∼3 to 4-fold over resting [Ca2+]i in response to hypoxia. Quinpirole (10 μM) significantly blunted the peak [Ca2+]i response to hypoxia. Repeat challenge with hypoxia plus 10 μM quinpirole in the presence of 10 μM sulpiride partially restored the hypoxia [Ca2+]i response. In sharp contrast to the older aged group, 10 μM quinpirole had minimal effect on hypoxia response of type 1 cells from 1-day-olds and a small but significant effect at 3 days of age. We conclude that stimulation of dopamine D2 receptors inhibits type 1 cell [Ca2+]i response to hypoxia, consistent with an inhibitory autoreceptor role. These findings suggest dopamine-mediated inhibition and oxygen sensitivity increase with age on a similar time course and do not support a role for dopamine as a major mediator of carotid chemoreceptor resetting.

scholarly journals Zn2+ Slows Down CaV3.3 Gating Kinetics: Implications for Thalamocortical Activity

2007 ◽  
Vol 98 (4) ◽  
pp. 2274-2284 ◽  
Author(s):  
M. Cataldi ◽  
V. Lariccia ◽  
V. Marzaioli ◽  
A. Cavaccini ◽  
G. Curia ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Whole Cell ◽  
Hek 293 ◽  
Gating Kinetics ◽  
Epileptiform Discharges ◽  
Whole Cell Patch Clamp ◽  
Recovery From Inactivation ◽  
293 Cells ◽  
Channel Opening ◽  
Current Activation

We employed whole cell patch-clamp recordings to establish the effect of Zn2+ on the gating the brain specific, T-type channel isoform CaV3.3 expressed in HEK-293 cells. Zn2+ (300 μM) modified the gating kinetics of this channel without influencing its steady-state properties. When inward Ca2+ currents were elicited by step depolarizations at voltages above the threshold for channel opening, current inactivation was significantly slowed down while current activation was moderately affected. In addition, Zn2+ slowed down channel deactivation but channel recovery from inactivation was only modestly changed. Zn2+ also decreased whole cell Ca2+ permeability to 45% of control values. In the presence of Zn2+, Ca2+ currents evoked by mock action potentials were more persistent than in its absence. Furthermore, computer simulation of action potential generation in thalamic reticular cells performed to model the gating effect of Zn2+ on T-type channels (while leaving the kinetic parameters of voltage-gated Na+ and K+ unchanged) revealed that Zn2+ increased the frequency and the duration of burst firing, which is known to depend on T-type channel activity. In line with this finding, we discovered that chelation of endogenous Zn2+ decreased the frequency of occurrence of ictal-like epileptiform discharges in rat thalamocortical slices perfused with medium containing the convulsant 4-aminopyridine (50 μM). These data demonstrate that Zn2+ modulates CaV3.3 channel gating thus leading to increased neuronal excitability. We also propose that endogenous Zn2+ may have a role in controlling thalamocortical oscillations.

No evidence for dependence of early cortical auditory processing on dopamine D2-receptor modulation: a whole-head magnetoencephalographic study

2001 ◽  
Vol 107 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Seppo Kähkönen ◽  
Jyrki Ahveninen ◽  
Eero Pekkonen ◽  
Seppo Kaakkola ◽  
Juha Huttunen ◽  
...  
Keyword(s):  
Auditory Processing ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Dopamine D2 ◽  
Receptor Modulation ◽  
Cortical Auditory Processing

scholarly journals Multiple-scale neuroendocrine signals connect brain and pituitary hormone rhythms

2017 ◽  
Vol 114 (9) ◽  
pp. 2379-2382 ◽  
Author(s):  
Nicola Romanò ◽  
Anne Guillou ◽  
David J. Hodson ◽  
Agnès O Martin ◽  
Patrice Mollard
Keyword(s):  
Time Window ◽  
Hormone Secretion ◽  
Multiple Scale ◽  
Building Blocks ◽  
Prolactin Secretion ◽  
Temporal Organization ◽  
Integration Time ◽  
Pituitary Hormone ◽  
Global Integration ◽  
Da Release

Small assemblies of hypothalamic “parvocellular” neurons release their neuroendocrine signals at the median eminence (ME) to control long-lasting pituitary hormone rhythms essential for homeostasis. How such rapid hypothalamic neurotransmission leads to slowly evolving hormonal signals remains unknown. Here, we show that the temporal organization of dopamine (DA) release events in freely behaving animals relies on a set of characteristic features that are adapted to the dynamic dopaminergic control of pituitary prolactin secretion, a key reproductive hormone. First, locally generated DA release signals are organized over more than four orders of magnitude (0.001 Hz–10 Hz). Second, these DA events are finely tuned within and between frequency domains as building blocks that recur over days to weeks. Third, an integration time window is detected across the ME and consists of high-frequency DA discharges that are coordinated within the minutes range. Thus, a hierarchical combination of time-scaled neuroendocrine signals displays local–global integration to connect brain–pituitary rhythms and pace hormone secretion.

Dopamine D2 Receptor Modulation of K+ Channel Activity Regulates Excitability of Nucleus Accumbens Neurons at Different Membrane Potentials

2006 ◽  
Vol 96 (5) ◽  
pp. 2217-2228 ◽  
Author(s):  
Mariela F. Perez ◽  
Francis J. White ◽  
Xiu-Ti Hu
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Brain Slices ◽  
Membrane Potentials ◽  
Inward Rectification ◽  
K Channel ◽  
Channel Activity ◽  
Receptor Modulation ◽  
Intracellular Ca

The nucleus accumbens (NAc) is a forebrain area in the mesocorticolimbic dopamine (DA) system that regulates many aspects of drug addiction. Neuronal activity in the NAc is modulated by different subtypes of DA receptors. Although DA signaling has received considerable attention, the mechanisms underlying D2-class receptor (D2R) modulation of firing in medium spiny neurons (MSNs) localized within the NAc remain ambiguous. In the present study, we performed whole cell current-clamp recordings in rat brain slices to determine whether and how D2R modulation of K+ channel activity regulates the intrinsic excitability of NAc neurons in the core region. D2R stimulation by quinpirole or DA significantly and dose-dependently decreased evoked Na+ spikes. This D2R effect on inhibiting evoked firing was abolished by antagonism of D2Rs, reversed by blockade of voltage-sensitive, slowly inactivating A-type K+ currents ( IAs), or eliminated by holding membrane potentials at levels in which IAs was inactivated. It was also mimicked by inhibition of cAMP-dependent protein kinase (PKA) activity, but not phosphatidylinositol-specific phospholipase C (PI-PLC) activity. Moreover, D2R stimulation also reduced the inward rectification and depolarized the resting membrane potentials (RMPs) by decreasing “leak” K+ currents. However, the D2R effects on inward rectification and RMP were blocked by inhibition of PI-PLC, but not PKA activity. These findings indicate that, with facilitated intracellular Ca2+ release and activation of the D2R/Gq/PLC/PIP2 pathway, the D2R-modulated changes in the NAc excitability are dynamically regulated and integrated by multiple K+ currents, including but are not limited to IAs, inwardly rectifying K+ currents ( IKir), and “leak” currents ( IK-2P).

Spike Timing-Dependent Plasticity: From Synapse to Perception

2006 ◽  
Vol 86 (3) ◽  
pp. 1033-1048 ◽  
Author(s):  
Yang Dan ◽  
Mu-Ming Poo
Keyword(s):  
Neuronal Excitability ◽  
Human Perception ◽  
Long Term Potentiation ◽  
Spike Timing ◽  
Spike Timing Dependent Plasticity ◽  
Dependent Plasticity ◽  
Functional Changes

Information in the nervous system may be carried by both the rate and timing of neuronal spikes. Recent findings of spike timing-dependent plasticity (STDP) have fueled the interest in the potential roles of spike timing in processing and storage of information in neural circuits. Induction of long-term potentiation (LTP) and long-term depression (LTD) in a variety of in vitro and in vivo systems has been shown to depend on the temporal order of pre- and postsynaptic spiking. Spike timing-dependent modification of neuronal excitability and dendritic integration was also observed. Such STDP at the synaptic and cellular level is likely to play important roles in activity-induced functional changes in neuronal receptive fields and human perception.

scholarly journals Disruption of cortical dopaminergic modulation impairs preparatory activity and delays licking initiation

2018 ◽  
Author(s):  
Ke Chen ◽  
Roberto Vincis ◽  
Alfredo Fontanini
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Cortex ◽  
Neural Activity ◽  
Cortical Activity ◽  
Motor Deficits ◽  
Receptor Modulation ◽  
Dopaminergic Modulation ◽  
Preparatory Activity ◽  
Motor Cortical

ABSTRACTDysfunction of motor cortices is thought to contribute to motor disorders such as Parkinson’s disease (PD). However, little is known on the link between cortical dopaminergic loss, abnormalities in motor cortex neural activity and motor deficits. We address the role of dopamine in modulating motor cortical activity by focusing on the anterior lateral motor cortex (ALM) of mice performing a cued-licking task. We first demonstrate licking deficits and concurrent alterations of spiking activity in ALM of mice with unilateral depletion of dopaminergic neurons (i.e., mice injected with 6-OHDA into the medial forebrain bundle). Hemi-lesioned mice displayed delayed licking initiation, shorter duration of licking bouts, and lateral deviation of tongue protrusions. In parallel with these motor deficits, we observed a reduction in the prevalence of cue responsive neurons and altered preparatory activity. Acute and local blockade of D1 receptors in ALM recapitulated some of the key behavioral and neural deficits observed in hemi-lesioned mice. Altogether, our data show a direct relationship between cortical D1 receptor modulation, cue-evoked and preparatory activity in ALM, and licking initiation.SIGNIFICANCE STATEMENTThe link between dopaminergic signaling, motor cortical activity and motor deficits is not fully understood. This manuscript describes alterations in neural activity of the anterior lateral motor cortex (ALM) that correlate with licking deficits in mice with unilateral dopamine depletion or with intra-ALM infusion of dopamine antagonist. The findings emphasize the importance of cortical dopaminergic modulation in motor initiation. These results will appeal not only to researchers interested in cortical control of licking, but also to a broader audience interested in motor control and dopaminergic modulation in physiological and pathological conditions. Specifically, our data suggest that dopamine deficiency in motor cortex could play a role in the pathogenesis of the motor symptoms of Parkinson’s disease.

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