Journal: Neuropsychopharmacology

Article Title: Neuregulin 3 Signaling Mediates Nicotine-Dependent Synaptic Plasticity in the Orbitofrontal Cortex and Cognition

doi: 10.1038/npp.2017.278

Figure Lengend Snippet: Nicotine effects on OFC neuroplasticity rely on NRG3/ErbB4 signaling. (a) A stimulation protocol, inducing LTP in control (ACSF) conditions results in LTD in the presence of NRG3 (2 nM) or nicotine (1 μM) (ACSF: n=12 slices, 5 mice; NRG3: n=6 slices, 3 mice; nicotine: n=7 slices, 3 mice). (b) DL-AP5 (50 μM) blocks LTP in normal ACSF but not LTD in ACSF supplemented by NRG3 (2 nM) or nicotine (1 μM) (AP5: n=7 slices, 3 mice; Nicotine+AP5: n=6 slices, 3 mice; NRG3+AP5: n=8 slices, 3 mice). (c) ErbB4 inhibitor afatinib (10 μM) attenuated both nicotine- and neuregulin induced LTD (NRG3+afatinib: n=6 slices, 3 mice; nicotine+afatinib: n=7 slices, 3 mice). Nicotine-induced LTD is also attenuated in a strain of NRG3ska mice that express reduced NRG3 levels (Nicotine (NRG3ska): n=7 slices, 3 mice). (d) Nicotine-induced LTD was attenuated by α7 nAChRs antagonist, αBTX (100 μM); α4β2*, antagonist, DHβE (1 μM); ryanodine-sensitive Ca2+ release blocker, ruthenium red (20 μM); or BACE1 inhibitor, LY2811376 (25 μM) (Nicotine+ αBTX: n=7 slices, 3 mice; Nicotine+DHβE: n=6 slices, 3 mice; Nicotine+ruthenium red: n=8 slices, 3 mice; Nicotine+LY2811376: n=9 slices, 4 mice). (e) fEPSP amplitudes in the last 10 min of recordings for treatment groups in a–d. Data are presented as mean±SEM. Data are analyzed by one-way ANOVAs followed by Bonferroni’s post hoc tests, or Student’s t-test. *p<0.05 vs ACSF; &p<0.05 vs NRG3; #p<0.05 vs nicotine.

Article Snippet: Animals and Housing Male B6/129F1 and NRG3 ska (Jackson Laboratories; 6–10 weeks of age; 20–25 g) were used in both the electrophysiology and molecular experiments.

Techniques: Control

Journal: Neuropsychopharmacology

Article Title: Neuregulin 3 Signaling Mediates Nicotine-Dependent Synaptic Plasticity in the Orbitofrontal Cortex and Cognition

doi: 10.1038/npp.2017.278

Figure Lengend Snippet: Molecular changes in the OFC of NRG3ska mice. (a) NRG3ska mice have reduced expression of NRG3 protein in the OFC compared to wild type controls. (b) ErbB4 mRNA is increased in the OFC of NRG3ska mice. (c) NRG1 and ErbB3 mRNA levels are similar in WT and NRG3ska mice. (d) The expression of nAChRs mRNA is unchanged in the NRG3ska mice. Protein levels of NRG3 or ErbB4 were normalized to GAPDH or β-tubulin, then normalized to WT controls. mRNA levels are normalized to WT controls. Data are presented as mean±SEM. n=8 for both WT and NRG3ska mice. Data are analyzed by Student’s t-tests. *p<0.05 compared to WT.

Article Snippet: Animals and Housing Male B6/129F1 and NRG3 ska (Jackson Laboratories; 6–10 weeks of age; 20–25 g) were used in both the electrophysiology and molecular experiments.

Techniques: Expressing

Journal: Neuropsychopharmacology

Article Title: Neuregulin 3 Signaling Mediates Nicotine-Dependent Synaptic Plasticity in the Orbitofrontal Cortex and Cognition

doi: 10.1038/npp.2017.278

Figure Lengend Snippet: A proposed model for nicotine-induced synaptic plasticity in the OFC. Nicotine activates Ca2+-permeable nAChRs, and Ca2+-sensitive ryanodine receptors (RyR). Increased intracellular Ca2+ enhances the proteolytic activity of BACE1, which directly cleaves NRG3. NRG3 binds to ErbB4 and increases GABA release. Nicotine also increases GABA uptake, presumably via an ErbB4-independent pathway. Increased vesicular GABA coupled with ErbB4-facilitated GABA release decreases excitability of post-synaptic pyramidal neurons and promotes LTD.

Article Snippet: Animals and Housing Male B6/129F1 and NRG3 ska (Jackson Laboratories; 6–10 weeks of age; 20–25 g) were used in both the electrophysiology and molecular experiments.

Techniques: Activity Assay