scholarly journals Mechanisms of Supralinear Calcium Integration in Dendrites of Hippocampal CA1 Fast-Spiking Cells

Author(s):  
Olivier Camiré ◽  
Ivan Lazarevich ◽  
Tommy Gilbert ◽  
Lisa Topolnik
Keyword(s):  
2020 ◽  
Author(s):  
Tyler G. Ekins ◽  
Vivek Mahadevan ◽  
Yajun Zhang ◽  
James A. D’Amour ◽  
Timothy Petros ◽  
...  

ABSTRACTType I lissencephaly is a neuronal migration disorder caused by haploinsuffiency of the LIS1 gene and is characterized in humans by agyria, mislamination of brain structures, developmental delays, and epilepsy. Here, we investigate the impact of LIS1 mutation on the cellular migration, morphophysiology, microcircuitry and genomics of mouse hippocampal CA1 parvalbumin-containing inhibitory interneurons (PV+INTs). We find that WT PV+INTs consist of two physiological subtypes (80% fast-spiking (FS), 20% non-fast-spiking (NFS)) and four morphological subtypes (basket, axo-axonic, bistratified, radiatum-targeting). We also discover that cell-autonomous mutations within interneurons disrupts morphological development of PV+INTs and results in the emergence of a non-canonical “intermediate spiking (IS)” subset of PV+INTs. In the GlobalLis mutant, IS/NFS cells become the dominant PV+INT subtypes (56%) and the percentage of FS cells shrinks to 44%. We also find that IS/NFS cells are prone to entering depolarizing block, causing them to temporarily lose the ability to initiate action potentials and control network excitation, potentially promoting seizures. Finally, single-cell nuclear RNAsequencing of PV+INTs revealed several misregulated genes related to morphogenesis, cellular excitability, and synapse formation.


2021 ◽  
Author(s):  
Maria Rita Karlocai ◽  
Judit Heredi ◽  
Tünde Benedek ◽  
Noemi Holderith ◽  
Andrea Lorincz ◽  
...  

AbstractThe molecular mechanisms underlying the diversity of cortical glutamatergic synapses is still only partially understood. Here, we tested the hypothesis that presynaptic active zones (AZs) are constructed from molecularly uniform, independent release sites (RSs), the number of which scales linearly with the AZ size. Paired recordings between hippocampal CA1 pyramidal cells and fast-spiking interneurons followed by quantal analysis demonstrate large variability in the number of RSs (N) at these connections. High resolution molecular analysis of functionally characterized synapses reveals highly variable Munc13-1 content of AZs that possess the same N. Replica immunolabeling also shows a 3-fold variability in the Munc13-1 content of AZs of identical size. Munc13-1 is clustered within the AZs; cluster size and density are also variable. Our results provide evidence for quantitative molecular heterogeneity of RSs and support a model in which the AZ is built up from variable numbers of molecularly heterogeneous, but independent RSs.


2016 ◽  
Vol 594 (4) ◽  
pp. 937-952 ◽  
Author(s):  
Andreas Bjorefeldt ◽  
Pontus Wasling ◽  
Henrik Zetterberg ◽  
Eric Hanse

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Maria Rita Karlocai ◽  
Judit Heredi ◽  
Tünde Benedek ◽  
Noemi Holderith ◽  
Andrea Lorincz ◽  
...  

The molecular mechanisms underlying the diversity of cortical glutamatergic synapses is still incompletely understood. Here, we tested the hypothesis that presynaptic active zones (AZs) are constructed from molecularly uniform, independent release sites (RSs), the number of which scales linearly with the AZ size. Paired recordings between hippocampal CA1 pyramidal cells and fast-spiking interneurons in acute slices from adult mice followed by quantal analysis demonstrate large variability in the number of RSs (N) at these connections. High resolution molecular analysis of functionally characterized synapses reveals variability in the content of one of the key vesicle priming factors – Munc13-1 – in AZs that possess the same N. Replica immunolabeling also shows a 3-fold variability in the total Munc13-1 content of AZs of identical size, and a 4-fold variability in the size and density of Munc13-1 clusters within the AZs. Our results provide evidence for quantitative molecular heterogeneity of RSs and support a model in which the AZ is built up from variable numbers of molecularly heterogeneous, but independent RSs.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tyler G Ekins ◽  
Vivek Mahadevan ◽  
Yajun Zhang ◽  
James A D'Amour ◽  
Gülcan Akgül ◽  
...  

Type I lissencephaly is a neuronal migration disorder caused by haploinsuffiency of the PAFAH1B1 (mouse: Pafah1b1) gene and is characterized by brain malformation, developmental delays, and epilepsy. Here, we investigate the impact of Pafah1b1 mutation on the cellular migration, morphophysiology, microcircuitry, and transcriptomics of mouse hippocampal CA1 parvalbumin-containing inhibitory interneurons (PV+INTs). We find that WT PV+INTs consist of two physiological subtypes (80% fast-spiking (FS), 20% non-fast-spiking (NFS)) and four morphological subtypes. We find that cell-autonomous mutations within interneurons disrupts morphophysiological development of PV+INTs and results in the emergence of a non-canonical ‘intermediate spiking (IS)’ subset of PV+INTs. We also find that now dominant IS/NFS cells are prone to entering depolarization block, causing them to temporarily lose the ability to initiate action potentials and control network excitation, potentially promoting seizures. Finally, single-cell nuclear RNAsequencing of PV+INTs revealed several misregulated genes related to morphogenesis, cellular excitability, and synapse formation.


2003 ◽  
Vol 90 (2) ◽  
pp. 655-665 ◽  
Author(s):  
Michael I. Anderson ◽  
Shane M. O'Mara

We examined neuronal activity in the dorsal subiculum of unrestrained, male adult Wistar rats, which were implanted with a moveable eight-electrode microdrive. The subiculum is the primary hippocampal formation output area and is comparatively uninvestigated neurophysiologically. We compared subicular unit activity and the subicular EEG while rats occupied a small, restricted environment and also correlated neuronal activity with the ongoing behavior of the animal. Units were separated using their electrophysiological characteristics into bursting units, regular spiking units, theta-modulated units, and fast spiking units. The bursting and regular spiking unit classes are similar to hippocampal CA1 units, whereas the fast spiking units appear to be interneurons. Bursting units were variable in their behavior: some units bursted regularly, and others bursted only occasionally. Theta-modulated units have not been described before; these were similar to regular spiking units in all respects except that they increased their firing significantly when theta oscillations were present in the simultaneous EEG record. Subicular EEG was similar to hippocampal EEG, with theta oscillations dominating “alert, moving” behaviors, while large amplitude irregular activity (LIA), which included sharp waves, predominated when theta oscillations were not present, mainly during “alert, still” and “quiet” behaviors. A relatively small proportion of subicular recordings (approximately 32%) were phase-locked to theta; this is a smaller proportion than in areas from which the subiculum takes major inputs. The relative lack of entrainment of subicular neurons by this important intrinsic rhythm is suggestive of a limit to which theta might be capable of affecting both subicular and hippocampal information processing more generally.


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