Eva Troyano-Rodriguez1, Celeste R Wirsig-Wiechmann1, Mohiuddin Ahmad2. 1. Department of Cell Biology and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. 2. Department of Cell Biology and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Electronic address: mohiuddin-ahmad@ouhsc.edu.
Abstract
BACKGROUND: Investigations in the neocortex have revealed that the balance of excitatory and inhibitory synaptic transmission (E/I ratio) is important for proper information processing. The disturbance of this balance underlies many neuropsychiatric illnesses, including autism spectrum disorder and schizophrenia. However, little is known about the contribution of E/I balance to the functioning of subcortical brain regions, such as the lateral septum (LS), a structure that plays important roles in regulating anxiety-related behavior. METHODS: We manipulated E/I balance in the mouse LS by localized conditional deletion of neuroligin-2, a postsynaptic cell adhesion protein located at gamma-aminobutyric acidergic synapses and important for inhibitory synaptic transmission. We then performed analyses of synaptic transmission in the LS, stress-induced expression of immediate early gene c-fos, and anxiety-related and depression-related behavior. RESULTS: The absence of neuroligin-2 in the LS in the mature mouse brain resulted in postsynaptic impairment of inhibitory synaptic transmission. Importantly, the reduced inhibition and resulting E/I imbalance decreased the responsiveness of LS neurons to stress. Furthermore, this E/I imbalance in the LS was associated with impaired stress-induced activation of downstream hypothalamic nuclei and reduced avoidance behavior of the animals in the elevated plus maze. CONCLUSIONS: Our results described the synaptic function of neuroligin-2 in the LS, uncovered a positive association between c-Fos-expressing neurons in the LS and downstream hypothalamic areas and avoidance behavior, and demonstrated that intact inhibitory synaptic transmission and proper E/I balance are required for the optimal functioning of this subcortical circuit.
BACKGROUND: Investigations in the neocortex have revealed that the balance of excitatory and inhibitory synaptic transmission (E/I ratio) is important for proper information processing. The disturbance of this balance underlies many neuropsychiatric illnesses, including autism spectrum disorder and schizophrenia. However, little is known about the contribution of E/I balance to the functioning of subcortical brain regions, such as the lateral septum (LS), a structure that plays important roles in regulating anxiety-related behavior. METHODS: We manipulated E/I balance in the mouse LS by localized conditional deletion of neuroligin-2, a postsynaptic cell adhesion protein located at gamma-aminobutyric acidergic synapses and important for inhibitory synaptic transmission. We then performed analyses of synaptic transmission in the LS, stress-induced expression of immediate early gene c-fos, and anxiety-related and depression-related behavior. RESULTS: The absence of neuroligin-2 in the LS in the mature mouse brain resulted in postsynaptic impairment of inhibitory synaptic transmission. Importantly, the reduced inhibition and resulting E/I imbalance decreased the responsiveness of LS neurons to stress. Furthermore, this E/I imbalance in the LS was associated with impaired stress-induced activation of downstream hypothalamic nuclei and reduced avoidance behavior of the animals in the elevated plus maze. CONCLUSIONS: Our results described the synaptic function of neuroligin-2 in the LS, uncovered a positive association between c-Fos-expressing neurons in the LS and downstream hypothalamic areas and avoidance behavior, and demonstrated that intact inhibitory synaptic transmission and proper E/I balance are required for the optimal functioning of this subcortical circuit.
Authors: Peter Jedlicka; Mrinalini Hoon; Theofilos Papadopoulos; Andreas Vlachos; Raphael Winkels; Alexandros Poulopoulos; Heinrich Betz; Thomas Deller; Nils Brose; Frédérique Varoqueaux; Stephan W Schwarzacher Journal: Cereb Cortex Date: 2010-06-07 Impact factor: 5.357
Authors: Olga Babaev; Paolo Botta; Elisabeth Meyer; Christian Müller; Hannelore Ehrenreich; Nils Brose; Andreas Lüthi; Dilja Krueger-Burg Journal: Neuropharmacology Date: 2015-06-30 Impact factor: 5.250