Ih blockade reduces cocaine-induced firing patterns of putative dopaminergic neurons of the ventral tegmental area in the anesthetized rat.

Published on Jan 10, 2022in Progress in Neuro-psychopharmacology & Biological Psychiatry5.067
· DOI :10.1016/J.PNPBP.2021.110431
Karl Bosque‐Cordero (UPR-RP: University of Puerto Rico, Río Piedras), Rafael Vázquez-Torres8
Estimated H-index: 8
+ 4 AuthorsCarlos A. Jiménez-Rivera13
Estimated H-index: 13
(University of Puerto Rico, Medical Sciences Campus)
Sources
Abstract
Abstract null null The hyperpolarization-activated cation current (Ih) is a determinant of intrinsic excitability in various cells, including dopaminergic neurons (DA) of the ventral tegmental area (VTA). In contrast to other cellular conductances, Ih is activated by hyperpolarization negative to -55 mV and activating Ih produces a time-dependent depolarizing current. Our laboratory demonstrated that cocaine sensitization, a chronic cocaine behavioral model, significantly reduces Ih amplitude in VTA DA neurons. Despite this reduction in Ih, the spontaneous firing of VTA DA cells after cocaine sensitization remained similar to control groups. Although the role of Ih in controlling VTA DA excitability is still poorly understood, our hypothesis is that Ih reduction could play a role of a homeostatic controller compensating for cocaine-induced change in excitability. Using in vivo single-unit extracellular electrophysiology in isoflurane anesthetized rats, we explored the contribution of Ih on spontaneous firing patterns of VTA DA neurons. A key feature of spontaneous excitability is bursting activity; bursting is defined as trains of two or more spikes occurring within a short interval and followed by a prolonged period of inactivity. Burst activity increases the reliability of information transfer. To elucidate the contribution of Ih to spontaneous firing patterns of VTA DA neurons, we locally infused an Ih blocker (ZD 7288, 8.3 μM) and evaluated its effect. Ih blockade significantly reduced firing rate, bursting frequency, and percent of spikes within a burst. In addition, Ih blockade significantly reduced acute cocaine-induced spontaneous firing rate, bursting frequency, and percent of spikes within a burst. Using whole-cell patch-clamp, we determine the progressive reduction of Ih after acute and chronic cocaine administration (15 mg/k.g intraperitoneally). Our data show a significant reduction (~25%) in Ih amplitude after 24 but not 2 h of acute cocaine administration. These results suggest that a progressive reduction of Ih could serve as a homeostatic regulator of cocaine-induced spontaneous firing patterns related to VTA DA excitability.
References72
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#1Bina Santoro (Columbia University)H-Index: 22
#2Mala M. Shah (UCL: University College London)H-Index: 20
The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are voltage-gated ion channels that critically modulate neuronal activity. Four HCN subunits (HCN1–4) have been cloned, each h...
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#1Bermary Santos-Vera (UPR: University of Puerto Rico)H-Index: 3
#2Ana del C. Vaquer-Alicea (UPR: University of Puerto Rico)H-Index: 1
Last. Carlos A. Jiménez-Rivera (UPR: University of Puerto Rico)H-Index: 13
view all 8 authors...
Abstract The Ih is a mixed depolarizing current present in neurons which, upon activation by hyperpolarization, modulates neuronal excitability in the mesocorticolimbic (MCL) system, an area which regulates emotions such as pleasure, reward, and motivation. Its biophysical properties are determined by HCN protein expression profiles, specifically HCN subunits 1–4. Previously, we reported that cocaine-induced behavioral sensitization increases HCN2 protein expression in all MCL areas with the Ven...
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#1Fleur Zeldenrust (Radboud University Nijmegen)H-Index: 8
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Neuronal action potentials or spikes provide a long-range, noise-resistant means of communication between neurons. As point processes single spikes contain little information in themselves, i.e. outside the context of spikes from other neurons. Moreover, they may fail to cross a synapse. A burst, which consists of a short high frequency train of spikes, will more reliably cross a synapse, increasing the likelihood of eliciting a postsynaptic spike, depending on the specific short-term plasticity...
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#1Peng Zhong (MCW: Medical College of Wisconsin)H-Index: 17
#2Casey R. Vickstrom (MCW: Medical College of Wisconsin)H-Index: 6
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: Dopamine neurons in the ventral tegmental area (VTA) are powerful regulators of depression-related behavior. Dopamine neuron activity is altered in chronic stress-based models of depression, but the underlying mechanisms remain incompletely understood. Here, we show that mice subject to chronic mild unpredictable stress (CMS) exhibit anxiety- and depressive-like behavior, which was associated with decreased VTA dopamine neuron firing in vivo and ex vivo. Dopamine neuron firing is governed by v...
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#1Tara Keck (UCL: University College London)H-Index: 16
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We summarize here the results presented and subsequent discussion from the meeting on Integrating Hebbian and Homeostatic Plasticity at the Royal Society in April 2016. We first outline the major themes and results presented at the meeting. We next provide a synopsis of the outstanding questions that emerged from the discussion at the end of the meeting and finally suggest potential directions of research that we believe are most promising to develop an understanding of how these two forms of pl...
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#1Francisco Arencibia-Albite (University of Puerto Rico, Medical Sciences Campus)H-Index: 6
#2Rafael Vázquez-Torres (University of Puerto Rico, Medical Sciences Campus)H-Index: 8
Last. Carlos A. Jiménez-Rivera (University of Puerto Rico, Medical Sciences Campus)H-Index: 13
view all 3 authors...
This work uses a new approach that directly extracts important biophysical parameters from alpha function-evoked synaptic potentials. Two of these parameters are the cell membrane capacitance (Cm) and rate at any time point of the synaptic waveform. The use of such methodology shows that cocaine sensitization reduces Cm and increases the speed of synaptic signaling. Paradoxically, although synaptic potentials show a faster decay under cocaine their temporal summation is substantially elevated.
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#1Meaghan C. Creed (University of Geneva)H-Index: 19
#2Jennifer Kaufling (CNRS: Centre national de la recherche scientifique)H-Index: 14
Last. Camilla Bellone (University of Geneva)H-Index: 28
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Potentiation of excitatory inputs onto dopamine neurons of the ventral tegmental area (VTA) induced by cocaine exposure allows remodeling of the mesocorticolimbic circuitry, which ultimately drives drug-adaptive behavior. This potentiation is mediated by changes in NMDAR and AMPAR subunit composition. It remains unknown how this synaptic plasticity affects the activity of dopamine neurons. Here, using rodents, we demonstrate that a single cocaine injection increases the firing rate and bursting ...
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#1Maria A. Mikhailova (Wake Forest University)H-Index: 4
#2Caroline E. Bass (UB: University at Buffalo)H-Index: 29
Last. Evgeny A. Budygin (Wake Forest University)H-Index: 32
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Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus a...
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#1Christoforos Tsantoulas ('KCL': King's College London)H-Index: 11
#2Elizabeth R. Mooney (University of Cambridge)H-Index: 3
Last. Peter A. McNaughton ('KCL': King's College London)H-Index: 59
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Nociception — the ability to detect painful stimuli — is an invaluable sense that warns against present or imminent damage. In patients with chronic pain, however, this warning signal persists in the absence of any genuine threat and affects all aspects of everyday life. Neuropathic pain, a form of chronic pain caused by damage to sensory nerves themselves, is dishearteningly refractory to drugs that may work in other types of pain and is a major unmet medical need begging for novel analgesics. ...
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#1Dominique Engel (University of Liège)H-Index: 17
#2Vincent Seutin (University of Liège)H-Index: 30
Key points The hyperpolarization-activated cation current Ih is expressed in dopamine neurons of the substantia nigra, but the subcellular distribution of the current and its role in synaptic integration remain unknown. We used cell-attached patch recordings to determine the localization profile of Ih along the somatodendritic axis of nigral dopamine neurons in slices from young rats. Ih density is higher in axon-bearing dendrites, in a membrane area close to the axon origin, than in the soma an...
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