| 1. |
- Arvidsson, Emma, 1986-, et al.
(författare)
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Age- and Sex-Dependence of Dopamine Release and Capacity for Recovery Identified in the Dorsal Striatum ofC57/Bl6J Mice
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e99592-
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Tidskriftsartikel (refereegranskat)abstract
- The dorsal striatum is the main input structure of the basal ganglia and the major target area of dopaminergic projections originating in the substantia nigra pars compacta. Heavily involved in the regulation of voluntary movement and habit formation, this structure is of strong importance in Parkinson's disease, obsessive-compulsive disorder, Tourette's syndrome and addiction. The C57/Bl6J mouse strain, the most commonly used strain in preclinical research today, is frequently used as a model organism for analysis of dopaminergic parameters implicated in human pathophysiology. Several components of the dopamine system have been shown to vary with age and sex, however knowledge of the contribution of these factors for dopamine release kinetics in the C57/Bl6J mouse strain is lacking. In the present study, we used an intracranial KCl-stimulation challenge paradigm to provoke release from dopaminergic terminals in the dorsal striatum of anaesthetized C57/Bl6J mice. By high-speed in vivo chronoamperometric recordings, we analyzed DA release parameters in male and female mice of two different ages. Our experiments demonstrate elevated DA amplitudes in adult compared to young mice of both sexes and higher DA amplitudes in females compared to males at both ages. Adult mice exhibited higher recovery capabilities after repeated stimulation than did young mice and also showed a lower variability in the kinetic parameters trise and t80 between stimulations. These results identified age- and sex- dimorphisms in DA release parameters and point to the importance of taking these dimorphisms into account when utilizing the C57/Bl6J mouse strain as model for neurological and neuropsychiatric disorders.
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| 2. |
- Hilscher, Markus M, et al.
(författare)
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Chrna2-OLM interneurons display different membrane properties and h-current magnitude depending on dorsoventral location
- 2019
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 29:12, s. 1224-1237
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampus is an extended structure displaying heterogeneous anatomical cell layers along its dorsoventral axis. It is known that dorsal and ventral regions show different integrity when it comes to functionality, innervation, gene expression, and pyramidal cell properties. Still, whether hippocampal interneurons exhibit different properties along the dorsoventral axis is not known. Here, we report electrophysiological properties of dorsal and ventral oriens lacunosum moleculare (OLM) cells from coronal sections of the Chrna2-cre mouse line. We found dorsal OLM cells to exhibit a significantly more depolarized resting membrane potential compared to ventral OLM cells, while action potential properties were similar between the two groups. We found ventral OLM cells to show a higher initial firing frequency in response to depolarizing current injections but also to exhibit a higher spike-frequency adaptation than dorsal OLM cells. Additionally, dorsal OLM cells displayed large membrane sags in response to negative current injections correlating with our results showing that dorsal OLM cells have more hyperpolarization-activated current (I-h) compared to ventral OLM cells. Immunohistochemical examination indicates the h-current to correspond to hyperpolarization-activated cyclic nucleotide-gated subunit 2 (HCN2) channels. Computational studies suggest that I-h in OLM cells is essential for theta oscillations in hippocampal circuits, and here we found dorsal OLM cells to present a higher membrane resonance frequency than ventral OLM cells. Thus, our results highlight regional differences in membrane properties between dorsal and ventral OLM cells allowing this interneuron to differently participate in the generation of hippocampal theta rhythms depending on spatial location along the dorsoventral axis of the hippocampus.
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| 3. |
- Hilscher, Markus M., 1987-, et al.
(författare)
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The alpha2 nicotinic acetylcholine receptor, a subunit with unique and selective expression in inhibitory interneurons associated with principal cells
- 2023
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Ingår i: Pharmacological Research. - : Elsevier. - 1043-6618 .- 1096-1186. ; 196
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Tidskriftsartikel (refereegranskat)abstract
- Nicotinic acetylcholine receptors (nAChRs) play crucial roles in various human disorders, with the α7, α4, α6, and α3-containing nAChR subtypes extensively studied in relation to conditions such as Alzheimer's disease, Parkinson's disease, nicotine dependence, mood disorders, and stress disorders. In contrast, the α2-nAChR subunit has received less attention due to its more restricted expression and the scarcity of specific agonists and antagonists for studying its function. Nevertheless, recent research has shed light on the unique expression pattern of the Chrna2 gene, which encodes the α2-nAChR subunit, and its involvement in distinct populations of inhibitory interneurons. This review highlights the structure, pharmacology, localization, function, and disease associations of α2-containing nAChRs and points to the unique expression pattern of the Chrna2 gene and its role in different inhibitory interneuron populations. These populations, including the oriens lacunosum moleculare (OLM) cells in the hippocampus, Martinotti cells in the neocortex, and Renshaw cells in the spinal cord, share common features and contribute to recurrent inhibitory microcircuits. Thus, the α2-nAChR subunit's unique expression pattern in specific interneuron populations and its role in recurrent inhibitory microcircuits highlight its importance in various physiological processes. Further research is necessary to uncover the comprehensive functionality of α2-containing nAChRs, delineate their specific contributions to neuronal circuits, and investigate their potential as therapeutic targets for related disorders.
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| 4. |
- Mikulovic, Sanja, 1986-, et al.
(författare)
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On the photovoltaic effect in localfield potential recordings
- 2016
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Ingår i: Neurophotonics. - 2329-423X. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- ptogenetics allows light activation of genetically defined cell populations and the study of their link to specific brain functions. While it is a powerful method that has revolutionized neuroscience in the last decade, the shortcomings of directly stimulating electrodes and living tissue with light have been poorly characterized. Here, we assessed the photovoltaic effects in local field potential (LFP) recordings of the mouse hippocampus. We found that light leads to several artifacts that resemble genuine LFP features in animals with no opsin expression, such as stereotyped peaks at the power spectrum, phase shifts across different recording channels, coupling between low and high oscillation frequencies, and sharp signal deflections that are detected as spikes. Further, we tested how light stimulation affected hippocampal LFP recordings in mice expressing channelrhodopsin 2 in parvalbumin neurons (PV/ChR2 mice). Genuine oscillatory activity at the frequency of light stimulation could not be separated from light-induced artifacts. In addition, light stimulation in PV/ChR2 mice led to an overall decrease in LFP power. Thus, genuine LFP changes caused by the stimulation of specific cell populations may be intermingled with spurious changes caused by photovoltaic effects. Our data suggest that care should be taken in the interpretation of electrophysiology experiments involving light stimulation.
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| 5. |
- Siwani, Samer, et al.
(författare)
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OLM alpha 2 Cells Bidirectionally Modulate Learning
- 2018
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Ingår i: Neuron. - : CELL PRESS. - 0896-6273 .- 1097-4199. ; 99:2, s. 404-412
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitory interneurons participate in mnemonic processes. However, defined roles for identified interneuron populations are scarce. A subpopulation of oriens lacunosum-moleculare (OLM) interneurons genetically defined by the expression of the nicotinic receptor alpha 2 subunit has been shown to gate information carried by either the temporoammonic pathway or Schaffer collaterals in vitro. Here we set out to determine whether selective modulation of OLM alpha 2 cells in the intermediate CA1 affects learning and memory in vivo. Our data show that intermediate OLM alpha 2 cells can either enhance (upon their inhibition) or impair (upon their activation) object memory encoding in freely moving mice, thus exerting bidirectional control. Moreover, we find that OLM alpha 2 cell activation inhibits fear-related memories and that OLM alpha 2 cells respond differently to nicotine in the dorsoventral axis. These results suggest that intermediate OLM alpha 2 cells are an important component in the CA1 microcircuit regulating learning and memory processes.
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| 6. |
- Winne, Jessica, et al.
(författare)
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Salicylate induces anxiety-like behavior and slow theta oscillation and abolishes the relationship between running speed and fast theta oscillation frequency
- 2019
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Ingår i: Hippocampus. - : WILEY. - 1050-9631 .- 1098-1063. ; 29:1, s. 15-25
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Tidskriftsartikel (refereegranskat)abstract
- Salicylate intoxication is a cause of tinnitus in humans and it is often used to produce tinnitus-like perception in animal models. Here, we assess whether salicylate induces anxiety-like electrophysiological and behavioral signs. Using microwire electrode arrays, we recorded local field potential in the ventral and, in some experiments dorsal hippocampus, in an open field arena 1 hr after salicylate (300 mg/kg) injection. We found that animals treated with salicylate moved dramatically less than saline treated animals. Salicylate-treated animals showed a strong 4-6 Hz (type 2) oscillation in the ventral hippocampus (with smaller peaks in dorsal hippocampus electrodes). Coherence in the 4-6 Hz-theta band was low in the ventral and dorsal hippocampus when compared to movement-related theta coherence (7-10 Hz). Moreover, movement related theta oscillation frequency decreased and its dependency on running speed was abolished. Our results suggest that salicylate-induced theta is mostly restricted to the ventral hippocampus. Slow theta has been classically associated to anxiety-like behaviors. Here, we show that salicylate application can consistently generate low frequency theta in the ventral hippocampus. Tinnitus and anxiety show strong comorbidity and the increase in ventral hippocampus low frequency theta could be part of this association.
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