scholarly journals An altered cognitive strategy associated with reduction of synaptic inhibition in the prefrontal cortex after social play deprivation in rats

2020 ◽  
Author(s):  
Azar Omrani ◽  
Ate Bijlsma ◽  
Marcia Spoelder ◽  
Jeroen P.H. Verharen ◽  
Lisa Bauer ◽  
...  

AbstractExperience-dependent organization of neuronal connectivity is a critical component of brain development, but how experience shapes prefrontal cortex (PFC) development is unknown. Here, we assessed how social play behaviour, which is highly abundant during post-weaning development, shapes PFC function and connectivity. We subjected juvenile rats to social play deprivation (SPD), followed by resocialization until adulthood. In a PFC-dependent probabilistic reversal learning task, SPD rats earned a similar number of rewards, but achieved more reversals than control rats. Computational trial-by-trial analysis showed that SPD rats displayed a simplified cognitive strategy. In addition, inhibitory synaptic currents were significantly reduced in layer 5 PFC cells of SPD rats, with specific changes in parvalbumin- and cannabinoid receptor 1-positive perisomatic inhibitory synapses. Thus, SPD has a long-lasting impact on PFC inhibition via synapse-specific alterations, associated with simplified cognitive strategies. We conclude that proper PFC development depends on pertinent social experience during a restricted time period.

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Daniel S. Miller ◽  
Kevin M. Wright

Abstract Background The development of functional neural circuits requires the precise formation of synaptic connections between diverse neuronal populations. The molecular pathways that allow GABAergic interneuron subtypes in the mammalian brain to initially recognize their postsynaptic partners remain largely unknown. The transmembrane glycoprotein Dystroglycan is localized to inhibitory synapses in pyramidal neurons, where it is required for the proper function of CCK+ interneurons. However, the precise temporal requirement for Dystroglycan during inhibitory synapse development has not been examined. Methods In this study, we use NEXCre or Camk2aCreERT2 to conditionally delete Dystroglycan from newly-born or adult pyramidal neurons, respectively. We then analyze forebrain development from postnatal day 3 through adulthood, with a particular focus on CCK+ interneurons. Results In the absence of postsynaptic Dystroglycan in developing pyramidal neurons, presynaptic CCK+ interneurons fail to elaborate their axons and largely disappear from the cortex, hippocampus, amygdala, and olfactory bulb during the first two postnatal weeks. Other interneuron subtypes are unaffected, indicating that CCK+ interneurons are unique in their requirement for postsynaptic Dystroglycan. Dystroglycan does not appear to be required in adult pyramidal neurons to maintain CCK+ interneurons. Bax deletion did not rescue CCK+ interneurons in Dystroglycan mutants during development, suggesting that they are not eliminated by canonical apoptosis. Rather, we observed increased innervation of the striatum, suggesting that the few remaining CCK+ interneurons re-directed their axons to neighboring areas where Dystroglycan expression remained intact. Conclusion Together these findings show that Dystroglycan functions as part of a synaptic partner recognition complex that is required early for CCK+ interneuron development in the forebrain.


2021 ◽  
Author(s):  
Daniel S Miller ◽  
Kevin M Wright

The development of functional neural circuits requires the precise formation of synaptic connections between diverse neuronal populations. The molecular pathways that allow GABAergic interneuron subtypes in the mammalian brain to recognize their postsynaptic partners remain largely unknown. The transmembrane glycoprotein Dystroglycan is localized to inhibitory synapses in pyramidal neurons, where it is required for the proper function of CCK+ interneurons. We show that deletion of Dystroglycan from pyramidal neurons selectively impairs CCK+ interneuron development during the first postnatal week. In the absence of postsynaptic Dystroglycan, presynaptic CCK+ interneurons fail to elaborate their axons and largely disappear from the cortex, hippocampus, amygdala, and olfactory bulb. Bax deletion did not rescue CCK+ interneurons, suggesting that they are not eliminated by canonical apoptosis in Dystroglycan mutants. Rather, we observed an increase in CCK+ interneuron innervation of the striatum, suggesting that the remaining CCK+ interneurons re-directed their axons to neighboring areas where Dystroglycan expression remained intact. Together these findings identify Dystroglycan as a critical regulator of CCK+ interneuron development.


2020 ◽  
Vol 29 (7) ◽  
pp. 616-622 ◽  
Author(s):  
Attila Oláh ◽  
Majid Alam ◽  
Jérémy Chéret ◽  
Nikolett Gréta Kis ◽  
Zoltán Hegyi ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexis Papariello ◽  
David Taylor ◽  
Ken Soderstrom ◽  
Karen Litwa

AbstractThe endocannabinoid system (ECS) plays a complex role in the development of neural circuitry during fetal brain development. The cannabinoid receptor type 1 (CB1) controls synaptic strength at both excitatory and inhibitory synapses and thus contributes to the balance of excitatory and inhibitory signaling. Imbalances in the ratio of excitatory to inhibitory synapses have been implicated in various neuropsychiatric disorders associated with dysregulated central nervous system development including autism spectrum disorder, epilepsy, and schizophrenia. The role of CB1 in human brain development has been difficult to study but advances in induced pluripotent stem cell technology have allowed us to model the fetal brain environment. Cortical spheroids resemble the cortex of the dorsal telencephalon during mid-fetal gestation and possess functional synapses, spontaneous activity, an astrocyte population, and pseudo-laminar organization. We first characterized the ECS using STORM microscopy and observed synaptic localization of components similar to that which is observed in the fetal brain. Next, using the CB1-selective antagonist SR141716A, we observed an increase in excitatory, and to a lesser extent, inhibitory synaptogenesis as measured by confocal image analysis. Further, CB1 antagonism increased the variability of spontaneous activity within developing neural networks, as measured by microelectrode array. Overall, we have established that cortical spheroids express ECS components and are thus a useful model for exploring endocannabinoid mediation of childhood neuropsychiatric disease.


2016 ◽  
Vol 332 ◽  
pp. 217-222 ◽  
Author(s):  
Katrina L. Toal ◽  
Kelly E. Radziwon ◽  
David P. Holfoth ◽  
Matthew A. Xu-Friedman ◽  
Micheal L. Dent

Sign in / Sign up

Export Citation Format

Share Document