@article{MTMT:3349431, title = {Single Bursts of Individual Granule Cells Functionally Rearrange Feedforward Inhibition}, url = {https://m2.mtmt.hu/api/publication/3349431}, author = {Neubrandt, Máté and Oláh, Viktor János and Brunner, János and Marosi, Endre Levente and Soltesz, Ivan and Szabadics, János}, doi = {10.1523/JNEUROSCI.1595-17.2018}, journal-iso = {J NEUROSCI}, journal = {JOURNAL OF NEUROSCIENCE}, volume = {38}, unique-id = {3349431}, issn = {0270-6474}, abstract = {The sparse single-spike activity of dentate gyrus granule cells (DG GCs) is punctuated by occasional brief bursts of 3- 7 action potentials. It is well-known that such presynaptic bursts in individual mossy fibers (MFs; axons of granule cells) are often able to discharge postsynaptic CA3 pyramidal cells due to powerful short-term facilitation. However, what happens in the CA3 network after the passage of a brief MF burst, before the arrival of the next burst or solitary spike, is not understood. Because MFs innervate significantly more CA3 interneurons than pyramidal cells, we focused on unitary MF responses in identified interneurons in the seconds-long postburst period, using paired recordings in rat hippocampal slices. Single bursts as short as 5 spikes in <30 ms in individual presynaptic MFs caused a sustained, large increase (tripling) in the amplitude of the unitary MF-EPSCs for several seconds in ivy, axo-axonic/chandelier and basket interneurons. The postburst unitary MF-EPSCs in these feedforward interneurons reached amplitudes that were even larger than the MF-EPSCs during the bursts in the same cells. In contrast, no comparable postburst enhancement of MF-EPSCs could be observed in pyramidal cells or nonfeed forward interneurons. The robust postburst increase in MF-EPSCs in feedforward interneurons was associated with significant shortening of the unitary synaptic delay and large downstream increases in disynaptic IPSCs in pyramidal cells. These results reveal a new cell type-specific plasticity that enables even solitary brief bursts in single GCs to powerfully enhance inhibition at the DG-CA3 interface in the seconds-long time-scales of interburst intervals.}, keywords = {Adolescent; hippocampus; ARTICLE; priority journal; controlled study; nonhuman; animal tissue; animal cell; HIPPOCAMPAL CA3 REGION; synaptic transmission; dentate gyrus; nerve cell plasticity; pyramidal nerve cell; interneuron; nerve cell excitability; granule cell; mossy fiber; feedback system; presynaptic nerve; feedforward inhibition; feedforward inhibition; Burst firing; rat}, year = {2018}, eissn = {1529-2401}, pages = {1711-1724}, orcid-numbers = {Oláh, Viktor János/0000-0002-2069-7525; Szabadics, János/0000-0002-4968-2562} } @article{MTMT:2941487, title = {Net Worth of Networks: Specificity in Anticonvulsant Action}, url = {https://m2.mtmt.hu/api/publication/2941487}, author = {Schneider, CJ and Soltesz, Ivan}, journal-iso = {EPILEPSY CURR}, journal = {EPILEPSY CURRENTS}, volume = {15}, unique-id = {2941487}, issn = {1535-7597}, keywords = {RESISTANCE; carbamazepine; ANTIEPILEPTIC DRUGS; GATED SODIUM-CHANNELS; CA1 NEURONS; CHRONIC EPILEPSY}, year = {2015}, eissn = {1535-7511}, pages = {45-46} } @article{MTMT:2941486, title = {Proton Radiation Alters Intrinsic and Synaptic Properties of CA1 Pyramidal Neurons of the Mouse Hippocampus}, url = {https://m2.mtmt.hu/api/publication/2941486}, author = {Sokolova, IV and Schneider, CJ and Bezaire, M and Soltesz, Ivan and Vlkolinsky, R and Nelson, GA}, doi = {10.1667/RR13785.1}, journal-iso = {RADIAT RES}, journal = {RADIATION RESEARCH}, volume = {183}, unique-id = {2941486}, issn = {0033-7587}, abstract = {High-energy protons constitute at least 85% of the fluence of energetic ions in interplanetary space. Although protons are only sparsely ionizing compared to higher atomic mass ions, they nevertheless significantly contribute to the delivered dose received by astronauts that can potentially affect central nervous system function at high fluence, especially during prolonged deep space missions such as to Mars. Here we report on the long-term effects of 1 Gy proton irradiation on electrophysiological properties of CA1 pyramidal neurons in the mouse hippocampus. The hippocampus is a key structure for the formation of long-term episodic memory, for spatial orientation and for information processing in a number of other cognitive tasks. CA1 pyramidal neurons form the last and critical relay point in the trisynaptic circuit of the hippocampal principal neurons through which information is processed before being transferred to other brain areas. Proper functioning of CA1 pyramidal neurons is crucial for hippocampus-dependent tasks. Using the patch-clamp technique to evaluate chronic effects of 1 Gy proton irradiation on CA1 pyramidal neurons, we found that the intrinsic membrane properties of CA1 pyramidal neurons were chronically altered at 3 months postirradiation, resulting in a hyperpolarization of the resting membrane potential (V-RMP) and a decrease in input resistance (R-in). These small but significant alterations in intrinsic properties decreased the excitability of CA1 pyramidal neurons, and had a dramatic impact on network function in a computational model of the CA1 microcircuit. We also found that proton-radiation exposure upregulated the persistent Na+ current (I-NaP) and increased the rate of miniature excitatory postsynaptic currents (mEPSCs). Both the I-NaP and the heightened rate of mEPSCs contribute to neuronal depolarization and excitation, and at least in part, could compensate for the reduced excitability resulting from the radiation effects on the V-RMP and the R-in. These results show long-term alterations in the intrinsic properties of CA1 pyramidal cells after realistic, low-dose proton irradiation. (C) 2015 by Radiation Research Society}, keywords = {IN-VIVO; NMDA receptor; AMYOTROPHIC-LATERAL-SCLEROSIS; COGNITIVE DEFICITS; REDOX MODULATORY SITE; PERSISTENT SODIUM CURRENT; FUNCTIONAL CONSEQUENCES; HOMEOSTATIC PLASTICITY; SPACE RADIATION; RECEPTOR-CHANNEL COMPLEX}, year = {2015}, eissn = {1938-5404}, pages = {208-218} } @article{MTMT:2941485, title = {Beyond the hammer and the scalpel: selective circuit control for the epilepsies}, url = {https://m2.mtmt.hu/api/publication/2941485}, author = {Krook-Magnuson, E and Soltesz, Ivan}, doi = {10.1038/nn.3943}, journal-iso = {NAT NEUROSCI}, journal = {NATURE NEUROSCIENCE}, volume = {18}, unique-id = {2941485}, issn = {1097-6256}, abstract = {Current treatment options for epilepsy are inadequate, as too many patients suffer from uncontrolled seizures and from negative side effects of treatment. In addition to these clinical challenges, our scientific understanding of epilepsy is incomplete. Optogenetic and designer receptor technologies provide unprecedented and much needed specificity, allowing for spatial, temporal and cell type-selective modulation of neuronal circuits. Using such tools, it is now possible to begin to address some of the fundamental unanswered questions in epilepsy, to dissect epileptic neuronal circuits and to develop new intervention strategies. Such specificity of intervention also has the potential for direct therapeutic benefits, allowing healthy tissue and network functions to continue unaffected. In this Perspective, we discuss promising uses of these technologies for the study of seizures and epilepsy, as well as potential use of these strategies for clinical therapies.}, keywords = {IN-VIVO; LONG-TERM; TRANSGENIC MICE; TEMPORAL-LOBE EPILEPSY; PROTEIN-COUPLED RECEPTORS; EPILEPTIFORM ACTIVITY; GENE-THERAPY; Optical control; Seizure suppression; LOOP OPTOGENETIC CONTROL}, year = {2015}, eissn = {1546-1726}, pages = {331-338} } @article{MTMT:2941484, title = {Resolution revolution: epilepsy dynamics at the microscale}, url = {https://m2.mtmt.hu/api/publication/2941484}, author = {Szabo, GG and Schneider, CJ and Soltesz, Ivan}, doi = {10.1016/j.conb.2014.12.012}, journal-iso = {CURR OPIN NEUROBIOL}, journal = {CURRENT OPINION IN NEUROBIOLOGY}, volume = {31}, unique-id = {2941484}, issn = {0959-4388}, abstract = {Our understanding of the neuronal mechanisms behind epilepsy dynamics has recently advanced due to the application of novel technologies, monitoring hundreds of neurons with single cell resolution. These developments have provided new theories on the relationship between physiological and pathological states, as well as common motifs for the propagation of paroxysmal activity. Although traditional electroencephalogram (EEG) recordings continue to describe normal network oscillations and abnormal epileptic events within and outside of the seizure focus, analysis of epilepsy dynamics at the microscale has found variability in the composition of macroscopically repetitive epileptiform events. These novel results point to heterogeneity in the underlying dynamics of the disorder, highlighting both the need and potential for more specific and targeted therapies.}, keywords = {TEMPORAL-LOBE EPILEPSY; PYRAMIDAL CELLS; focal epilepsy; High-frequency oscillations; FAST RIPPLES; PEDIATRIC EPILEPSY; Intracranial EEG; HUB NEURONS; 80-500 HZ; OPTOGENETIC CONTROL}, year = {2015}, eissn = {1873-6882}, pages = {239-243} } @article{MTMT:2941483, title = {Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy}, url = {https://m2.mtmt.hu/api/publication/2941483}, author = {Soltesz, Ivan and Alger, BE and Kano, M and Lee, SH and Lovinger, DM and Ohno-Shosaku, T and Watanabe, M}, doi = {10.1038/nrn3937}, journal-iso = {NAT REV NEUROSCI}, journal = {NATURE REVIEWS NEUROSCIENCE}, volume = {16}, unique-id = {2941483}, issn = {1471-003X}, abstract = {Endocannabinoids are lipid-derived messengers, and both their synthesis and breakdown are under tight spatiotemporal regulation. As retrograde signalling molecules, endocannabinoids are synthesized postsynaptically but activate presynaptic cannabinoid receptor 1 (CB1) receptors to inhibit neurotransmitter release. In turn, CB1-expressing inhibitory and excitatory synapses act as strategically placed control points for activity-dependent regulation of dynamically changing normal and pathological oscillatory network activity. Here, we highlight emerging principles of cannabinoid circuit control and plasticity, and discuss their relevance for epilepsy and related comorbidities. New insights into cannabinoid signalling may facilitate the translation of the recent interest in cannabis-related substances as antiseizure medications to evidence-based treatment strategies.}, keywords = {LONG-TERM DEPRESSION; TEMPORAL-LOBE EPILEPSY; HIPPOCAMPAL PYRAMIDAL CELLS; FRAGILE-X-SYNDROME; ENDOCANNABINOID SYSTEM; ENDOGENOUS CANNABINOIDS; PHOSPHOLIPASE-C-BETA; IN-VIVO EXPOSURE; SPIKING BASKET CELLS; DIACYLGLYCEROL LIPASE-ALPHA}, year = {2015}, eissn = {1471-0048}, pages = {264-277} } @article{MTMT:2941482, title = {In vivo evaluation of the dentate gate theory in epilepsy}, url = {https://m2.mtmt.hu/api/publication/2941482}, author = {Krook-Magnuson, E and Armstrong, C and Bui, A and Lew, S and Oijala, M and Soltesz, Ivan}, doi = {10.1113/JP270056}, journal-iso = {J PHYSIOL-LONDON}, journal = {JOURNAL OF PHYSIOLOGY-LONDON}, volume = {593}, unique-id = {2941482}, issn = {0022-3751}, abstract = {The dentate gyrus is a region subject to intense study in epilepsy because of its posited role as a gate', acting to inhibit overexcitation in the hippocampal circuitry through its unique synaptic, cellular and network properties that result in relatively low excitability. Numerous changes predicted to produce dentate hyperexcitability are seen in epileptic patients and animal models. However, recent findings question whether changes are causative or reactive, as well as the pathophysiological relevance of the dentate in epilepsy. Critically, direct in vivo modulation of dentate gate' function during spontaneous seizure activity has not been explored. Therefore, using a mouse model of temporal lobe epilepsy with hippocampal sclerosis, a closed-loop system and selective optogenetic manipulation of granule cells during seizures, we directly tested the dentate gate' hypothesis in vivo. Consistent with the dentate gate theory, optogenetic gate restoration through granule cell hyperpolarization efficiently stopped spontaneous seizures. By contrast, optogenetic activation of granule cells exacerbated spontaneous seizures. Furthermore, activating granule cells in non-epileptic animals evoked acute seizures of increasing severity. These data indicate that the dentate gyrus is a critical node in the temporal lobe seizure network, and provide the first in vivo support for the dentate gate' hypothesis.}, keywords = {LONG-TERM; KAINIC ACID; TEMPORAL-LOBE EPILEPSY; seizure frequency; EPILEPTIFORM ACTIVITY; GYRUS; PATTERN SEPARATION; MOUSE HIPPOCAMPUS; OPTOGENETIC CONTROL; HIPPOCAMPAL GRANULE CELLS}, year = {2015}, eissn = {1469-7793}, pages = {2379-2388} } @article{MTMT:2941481, title = {Administration of CoQ10 analogue ameliorates dysfunction of the mitochondrial respiratory chain in a mouse model of Angelman Syndrome (vol 76, pg 77, 2015)}, url = {https://m2.mtmt.hu/api/publication/2941481}, author = {Llewellyn, KJ and Nalbandian, A and Gomez, A and Wei, D and Walker, N and Bui, A and Kim, H and Soltesz, Ivan and Kimonis, VE}, doi = {10.1016/j.nbd.2015.03.024}, journal-iso = {NEUROBIOL DIS}, journal = {NEUROBIOLOGY OF DISEASE}, volume = {78}, unique-id = {2941481}, issn = {0969-9961}, year = {2015}, eissn = {1095-953X}, pages = {56-56} } @article{MTMT:2941480, title = {Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy (vol 16, pg 264, 2015)}, url = {https://m2.mtmt.hu/api/publication/2941480}, author = {Soltesz, Ivan and Alger, BE and Kano, M and Lee, SH and Lovinger, DM and Ohno-Shosaku, T and Watanabe, M}, doi = {10.1038/nrn3974}, journal-iso = {NAT REV NEUROSCI}, journal = {NATURE REVIEWS NEUROSCIENCE}, volume = {16}, unique-id = {2941480}, issn = {1471-003X}, year = {2015}, eissn = {1471-0048}, pages = {327-328} } @article{MTMT:2941479, title = {Neuroelectronics and Biooptics Closed-Loop Technologies in Neurological Disorders}, url = {https://m2.mtmt.hu/api/publication/2941479}, author = {Krook-Magnuson, E and Gelinas, JN and Soltesz, Ivan and Buzsaki, G}, doi = {10.1001/jamaneurol.2015.0608}, journal-iso = {JAMA NEUROL}, journal = {JAMA NEUROLOGY}, volume = {72}, unique-id = {2941479}, issn = {2168-6149}, abstract = {Brain-implanted devices are no longer a futuristic idea. Traditionally, therapies for most neurological disorders are adjusted based on changes in clinical symptoms and diagnostic measures observed over time. These therapies are commonly pharmacological or surgical, requiring continuous or irreversible treatment regimens that cannot respond rapidly to fluctuations of symptoms or isolated episodes of dysfunction. In contrast, closed-loop systems provide intervention only when needed by detecting abnormal neurological signals and modulating them with instantaneous feedback. Closed-loop systems have been applied to several neurological conditions (most notably epilepsy and movement disorders), but widespread use is limited by conceptual and technical challenges. Herein, we discuss how advances in experimental closed-loop systems hold promise for improved clinical benefit in patients with neurological disorders.}, keywords = {IN-VIVO; PARKINSONS-DISEASE; EPILEPSY; TREMOR; DEEP BRAIN-STIMULATION; subthalamic nucleus; DIRECT-CURRENT STIMULATION; SCAN CYCLIC VOLTAMMETRY; OPTOGENETIC CONTROL; BISPECTRAL INDEX}, year = {2015}, eissn = {2168-6157}, pages = {823-829} }