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1.
Front Neuroinform ; 17: 1005936, 2023.
Article in English | MEDLINE | ID: mdl-36970656

ABSTRACT

The rapid effects of estradiol on membrane receptors are in the focus of the estradiol research field, however, the molecular mechanisms of these non-classical estradiol actions are poorly understood. Since the lateral diffusion of membrane receptors is an important indicator of their function, a deeper understanding of the underlying mechanisms of non-classical estradiol actions can be achieved by investigating receptor dynamics. Diffusion coefficient is a crucial and widely used parameter to characterize the movement of receptors in the cell membrane. The aim of this study was to investigate the differences between maximum likelihood-based estimation (MLE) and mean square displacement (MSD) based calculation of diffusion coefficients. In this work we applied both MSD and MLE to calculate diffusion coefficients. Single particle trajectories were extracted from simulation as well as from α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor tracking in live estradiol-treated differentiated PC12 (dPC12) cells. The comparison of the obtained diffusion coefficients revealed the superiority of MLE over the generally used MSD analysis. Our results suggest the use of the MLE of diffusion coefficients because as it has a better performance, especially for large localization errors or slow receptor movements.

2.
Front Neuroanat ; 16: 779390, 2022.
Article in English | MEDLINE | ID: mdl-36003850

ABSTRACT

Layer I of the medial entorhinal cortex (MEC) contains converging axons from several brain areas and dendritic tufts originating from principal cells located in multiple layers. Moreover, specific GABAergic interneurons are also located in the area, but their inputs, outputs, and effect on local network events remain elusive. Neurogliaform cells are the most frequent and critically positioned inhibitory neurons in layer I. They are considered to conduct feed-forward inhibition via GABAA and GABAB receptors on pyramidal cells located in several cortical areas. Using optogenetic experiments, we showed that layer I neurogliaform cells receive excitatory inputs from layer II pyramidal cells, thereby playing a critical role in local feedback inhibition in the MEC. We also found that neurogliaform cells are evenly distributed in layer I and do not correlate with the previously described compartmentalization ("cell islands") of layer II. We concluded that the activity of neurogliaform cells in layer I is largely set by layer II pyramidal cells through excitatory synapses, potentially inhibiting the apical dendrites of all types of principal cells in the MEC.

3.
Front Endocrinol (Lausanne) ; 13: 993552, 2022.
Article in English | MEDLINE | ID: mdl-36686456

ABSTRACT

The striatum is an essential component of the basal ganglia that is involved in motor control, action selection and motor learning. The pathophysiological changes of the striatum are present in several neurological and psychiatric disorder including Parkinson's and Huntington's diseases. The striatal cholinergic neurons are the main regulators of striatal microcircuitry. It has been demonstrated that estrogen exerts various effects on neuronal functions in dopaminergic and medium spiny neurons (MSN), however little is known about how the activity of cholinergic interneurons are influenced by estrogens. In this study we examined the acute effect of 17ß-estradiol on the function of striatal cholinergic neurons in adult mice in vitro. We also tested the effect of estrus cycle and sex on the spontaneous activity of cholinergic interneurons in the striatum. Our RNAscope experiments showed that ERα, ERß, and GPER1 receptor mRNAs are expressed in some striatal cholinergic neurons at a very low level. In cell-attached patch clamp experiments, we found that a high dose of 17ß-estradiol (100 nM) affected the spontaneous firing rate of these neurons only in old males. Our findings did not demonstrate any acute effect of a low concentration of 17ß-estradiol (100 pM) or show any association of estrus cycle or sex with the activity of striatal cholinergic neurons. Although estrogen did not induce changes in the intrinsic properties of neurons, indirect effects via modulation of the synaptic inputs of striatal cholinergic interneurons cannot be excluded.


Subject(s)
Cholinergic Agents , Interneurons , Male , Female , Mice , Animals , Interneurons/physiology , Cholinergic Agents/pharmacology , Cholinergic Neurons/physiology , Estradiol/pharmacology , Estrogens
4.
Proc Natl Acad Sci U S A ; 118(40)2021 10 05.
Article in English | MEDLINE | ID: mdl-34599103

ABSTRACT

Circuit formation in the central nervous system has been historically studied during development, after which cell-autonomous and nonautonomous wiring factors inactivate. In principle, balanced reactivation of such factors could enable further wiring in adults, but their relative contributions may be circuit dependent and are largely unknown. Here, we investigated hippocampal mossy fiber sprouting to gain insight into wiring mechanisms in mature circuits. We found that sole ectopic expression of Id2 in granule cells is capable of driving mossy fiber sprouting in healthy adult mouse and rat. Mice with the new mossy fiber circuit solved spatial problems equally well as controls but appeared to rely on local rather than global spatial cues. Our results demonstrate reprogrammed connectivity in mature neurons by one defined factor and an assembly of a new synaptic circuit in adult brain.


Subject(s)
Inhibitor of Differentiation Protein 2/genetics , Transcription, Genetic/genetics , Animals , Epilepsy, Temporal Lobe/genetics , Mice , Mossy Fibers, Hippocampal/physiology , Neurogenesis/genetics , Rats
5.
Commun Biol ; 3(1): 754, 2020 12 10.
Article in English | MEDLINE | ID: mdl-33303963

ABSTRACT

GABA released from heterogeneous types of interneurons acts in a complex spatio-temporal manner on postsynaptic targets in the networks. In addition to GABA, a large fraction of GABAergic cells also express neuromodulator peptides. Somatostatin (SOM) containing interneurons, in particular, have been recognized as key players in several brain circuits, however, the action of SOM and its downstream network effects remain largely unknown. Here, we used optogenetics, electrophysiologic, anatomical and behavioral experiments to reveal that the dendrite-targeting, SOM+ GABAergic interneurons demonstrate a unique layer-specific action in the medial entorhinal cortex (MEC) both in terms of GABAergic and SOM-related properties. We show that GABAergic and somatostatinergic neurotransmission originating from SOM+ local interneurons preferentially inhibit layerIII-V pyramidal cells, known to be involved in memory formation. We propose that this dendritic GABA-SOM dual inhibitory network motif within the MEC serves to selectively modulate working-memory formation without affecting the retrieval of already learned spatial navigation tasks.


Subject(s)
Entorhinal Cortex/metabolism , GABAergic Neurons/metabolism , Gene Expression , Interneurons/metabolism , Pyramidal Cells/metabolism , Somatostatin/genetics , Animals , Biomarkers , Cell Communication , Electrophysiological Phenomena , Female , Male , Memory, Short-Term , Mice , Mice, Knockout , Neural Pathways , Neurotransmitter Agents/biosynthesis , Peptides/metabolism , Somatostatin/metabolism , Synaptic Transmission
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