| First Author | Troyano-Rodriguez E | Year | 2019 |
| Journal | Biol Psychiatry | Volume | 85 |
| Issue | 12 | Pages | 1046-1055 |
| PubMed ID | 30878196 | Mgi Jnum | J:292403 |
| Mgi Id | MGI:6445067 | Doi | 10.1016/j.biopsych.2019.01.022 |
| Citation | Troyano-Rodriguez E, et al. (2019) Neuroligin-2 Determines Inhibitory Synaptic Transmission in the Lateral Septum to Optimize Stress-Induced Neuronal Activation and Avoidance Behavior. Biol Psychiatry 85(12):1046-1055 |
| abstractText | 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. |
