scholarly journals Genetic dissection of the glutamatergic neuron system in cerebral cortex

Nature ◽  
2021 ◽  
Vol 598 (7879) ◽  
pp. 182-187 ◽  
Author(s):  
Katherine S. Matho ◽  
Dhananjay Huilgol ◽  
William Galbavy ◽  
Miao He ◽  
Gukhan Kim ◽  
...  

AbstractDiverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels.

Author(s):  
Katherine S. Matho ◽  
Dhananjay Huilgol ◽  
William Galbavy ◽  
Gukhan Kim ◽  
Miao He ◽  
...  

ABSTRACTDiverse types of glutamatergic pyramidal neurons (PyNs) mediate the myriad processing streams and output channels of the cerebral cortex, yet all derive from neural progenitors of the embryonic dorsal telencephalon. Here, we establish genetic strategies and tools for dissecting and fate mapping PyN subpopulations based on their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target the temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen of temporally inducible mouse Cre and Flp knock-in driver lines to enable combinatorial targeting of major progenitor types and projection classes. Intersectional converter lines confer viral access to specific subsets defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for multi-modal characterization of PyN subpopulations and tracking their developmental trajectories toward elucidating the organization and assembly of cortical processing networks and output channels.


Science ◽  
2012 ◽  
Vol 337 (6095) ◽  
pp. 746-749 ◽  
Author(s):  
S. J. Franco ◽  
C. Gil-Sanz ◽  
I. Martinez-Garay ◽  
A. Espinosa ◽  
S. R. Harkins-Perry ◽  
...  

2021 ◽  
Vol 17 (9) ◽  
pp. e1009416
Author(s):  
Eduarda Susin ◽  
Alain Destexhe

Gamma oscillations are widely seen in the awake and sleeping cerebral cortex, but the exact role of these oscillations is still debated. Here, we used biophysical models to examine how Gamma oscillations may participate to the processing of afferent stimuli. We constructed conductance-based network models of Gamma oscillations, based on different cell types found in cerebral cortex. The models were adjusted to extracellular unit recordings in humans, where Gamma oscillations always coexist with the asynchronous firing mode. We considered three different mechanisms to generate Gamma, first a mechanism based on the interaction between pyramidal neurons and interneurons (PING), second a mechanism in which Gamma is generated by interneuron networks (ING) and third, a mechanism which relies on Gamma oscillations generated by pacemaker chattering neurons (CHING). We find that all three mechanisms generate features consistent with human recordings, but that the ING mechanism is most consistent with the firing rate change inside Gamma bursts seen in the human data. We next evaluated the responsiveness and resonant properties of these networks, contrasting Gamma oscillations with the asynchronous mode. We find that for both slowly-varying stimuli and precisely-timed stimuli, the responsiveness is generally lower during Gamma compared to asynchronous states, while resonant properties are similar around the Gamma band. We could not find conditions where Gamma oscillations were more responsive. We therefore predict that asynchronous states provide the highest responsiveness to external stimuli, while Gamma oscillations tend to overall diminish responsiveness.


2019 ◽  
Vol 51 (4) ◽  
pp. 234-243 ◽  
Author(s):  
Mariko Tada ◽  
Kenji Kirihara ◽  
Daisuke Koshiyama ◽  
Mao Fujioka ◽  
Kaori Usui ◽  
...  

Altered gamma oscillations have attracted considerable attention as an index of the excitation/inhibition (E/I) imbalance in schizophrenia and other neuropsychiatric disorders. The auditory steady-state response (ASSR) has been the most robust probe of abnormal gamma oscillatory dynamics in schizophrenia. Here, we review recent ASSR studies in patients with schizophrenia and other neuropsychiatric disorders. Preclinical ASSR research, which has contributed to the elucidation of the underlying pathophysiology of these diseases, is also discussed. The developmental trajectory of the ASSR has been explored and may show signs of the maturation and disruption of E/I balance in adolescence. Animal model studies have shown that synaptic interactions between parvalbumin-positive GABAergic interneurons and pyramidal neurons contribute to the regulation of E/I balance, which is related to the generation of gamma oscillation. Therefore, ASSR alteration may be a significant electrophysiological finding related to the E/I imbalance in neuropsychiatric disorders, which is a cross-disease feature and may reflect clinical staging. Future studies regarding ASSR generation, especially in nonhuman primate models, will advance our understanding of the brain circuit and the molecular mechanisms underlying neuropsychiatric disorders.


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