scholarly journals CaV2.1 ablation in cortical interneurons selectively impairs fast-spiking basket cells and causes generalized seizures

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Elsa Rossignol ◽  
Illya Kruglikov ◽  
Arn M. J. M. van den Maagdenberg ◽  
Bernardo Rudy ◽  
Gord Fishell
2015 ◽  
Vol 113 (6) ◽  
pp. 1850-1861 ◽  
Author(s):  
Diana C. Rotaru ◽  
Cameron Olezene ◽  
Takeaki Miyamae ◽  
Nadezhda V. Povysheva ◽  
Aleksey V. Zaitsev ◽  
...  

In rodent cortex GABAA receptor (GABAAR)-mediated synapses are a significant source of input onto GABA neurons, and the properties of these inputs vary among GABA neuron subtypes that differ in molecular markers and firing patterns. Some features of cortical interneurons are different between rodents and primates, but it is not known whether inhibition of GABA neurons is prominent in the primate cortex and, if so, whether these inputs show heterogeneity across GABA neuron subtypes. We thus studied GABAAR-mediated miniature synaptic events in GABAergic interneurons in layer 3 of monkey dorsolateral prefrontal cortex (DLPFC). Interneurons were identified on the basis of their firing pattern as fast spiking (FS), regular spiking (RS), burst spiking (BS), or irregular spiking (IS). Miniature synaptic events were common in all of the recorded interneurons, and the frequency of these events was highest in FS neurons. The amplitude and kinetics of miniature inhibitory postsynaptic potentials (mIPSPs) also differed between DLPFC interneuron subtypes in a manner correlated with their input resistance and membrane time constant. FS neurons had the fastest mIPSP decay times and the strongest effects of the GABAAR modulator zolpidem, suggesting that the distinctive properties of inhibitory synaptic inputs onto FS cells are in part conferred by GABAARs containing α1 subunits. Moreover, mIPSCs differed between FS and RS interneurons in a manner consistent with the mIPSP findings. These results show that in the monkey DLPFC GABAAR-mediated synaptic inputs are prominent in layer 3 interneurons and may differentially regulate the activity of different interneuron subtypes.


2011 ◽  
Vol 106 (2) ◽  
pp. 775-787 ◽  
Author(s):  
Matthew S. Lazarus ◽  
Z. Josh Huang

In the rodent primary visual cortex, maturation of GABA inhibitory circuitry is regulated by visual input and contributes to the onset and progression of ocular dominance (OD) plasticity. Cortical inhibitory circuitry consists of diverse groups of GABAergic interneurons, which display distinct physiological properties and connectivity patterns. Whether different classes of interneurons mature with similar or distinct trajectories and how their maturation profiles relate to experience dependent development are not well understood. We used green fluorescent protein reporter lines to study the maturation of two broad classes of cortical interneurons: parvalbumin-expressing (PV) cells, which are fast spiking and innervate the soma and proximal dendrites, and somatostatin-expressing (SOM) cells, which are regular spiking and target more distal dendrites. Both cell types demonstrate extensive physiological maturation, but with distinct trajectories, from eye opening to the peak of OD plasticity. Typical fast-spiking characteristics of PV cells became enhanced, and synaptic signaling from PV to pyramidal neurons became faster. SOM cells demonstrated a large increase in input resistance and a depolarization of resting membrane potential, resulting in increased excitability. While the substantial maturation of PV cells is consistent with the importance of this source of inhibition in triggering OD plasticity, the significant increase in SOM cell excitability suggests that dendrite-targeted inhibition may also play a role in OD plasticity. More generally, these results underscore the necessity of cell type-based analysis and demonstrate that distinct classes of cortical interneurons have markedly different developmental profiles, which may contribute to the progressive emergence of distinct functional properties of cortical circuits.


2019 ◽  
Author(s):  
Ruchi Malik ◽  
Emily Ling-Lin Pai ◽  
Anna N Rubin ◽  
April M Stafford ◽  
Kartik Angara ◽  
...  

AbstractMedial ganglionic eminence (MGE)-derived somatostatin (SST)+ and parvalbumin (PV)+ cortical interneurons (CINs), have characteristic molecular, anatomical and physiological properties. However, mechanisms regulating their diversity remain poorly understood. Here, we show that conditional loss of the Tuberous Sclerosis (TS) gene, Tsc1, which inhibits mammalian target of rapamycin (MTOR), causes a subset of SST+ CINs, to express PV and adopt fast-spiking (FS) properties, characteristic of PV+ CINs. These changes also occur when only one allele of Tsc1 is deleted, making these findings relevant to individuals with TS. Notably, treatment with rapamycin, which inhibits MTOR, reverses these changes in adult mice. These data reveal novel functions of MTOR signaling in regulating PV expression and FS properties, which may contribute to some neuropsychiatric symptoms observed in TS. Moreover, they suggest that CINs can exhibit properties intermediate between those classically associated with PV+ or SST+ CINs, which may be dynamically regulated by the MTOR signaling.


2008 ◽  
Vol 586 (8) ◽  
pp. 2061-2075 ◽  
Author(s):  
Yexica Aponte ◽  
Josef Bischofberger ◽  
Peter Jonas

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ruchi Malik ◽  
Emily Ling-Lin Pai ◽  
Anna N Rubin ◽  
April M Stafford ◽  
Kartik Angara ◽  
...  

Abstract Medial ganglionic eminence (MGE)-derived somatostatin (SST)+ and parvalbumin (PV)+ cortical interneurons (CINs), have characteristic molecular, anatomical and physiological properties. However, mechanisms regulating their diversity remain poorly understood. Here, we show that conditional loss of the Tuberous Sclerosis Complex (TSC) gene, Tsc1, which inhibits the mammalian target of rapamycin (MTOR), causes a subset of SST+ CINs, to express PV and adopt fast-spiking (FS) properties, characteristic of PV+ CINs. Milder intermediate phenotypes also occur when only one allele of Tsc1 is deleted. Notably, treatment of adult mice with rapamycin, which inhibits MTOR, reverses the phenotypes. These data reveal novel functions of MTOR signaling in regulating PV expression and FS properties, which may contribute to TSC neuropsychiatric symptoms. Moreover, they suggest that CINs can exhibit properties intermediate between those classically associated with PV+ or SST+ CINs, which may be dynamically regulated by the MTOR signaling.


2007 ◽  
Vol 3 (8) ◽  
pp. e156 ◽  
Author(s):  
David Golomb ◽  
Karnit Donner ◽  
Liron Shacham ◽  
Dan Shlosberg ◽  
Yael Amitai ◽  
...  

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