Journal: bioRxiv

Article Title: Ketamine rescues anhedonia by cell-type and input specific adaptations in the Nucleus Accumbens

doi: 10.1101/2023.06.08.544088

Figure Lengend Snippet: a , d , h, Experimental timelines. b, Cumulative probability plots of the amplitudes (left) or frequencies (center) of sEPSCs recorded from NAc D1-MSNs in brain slices from stress-naïve mice ( n = 20 cells; 10 mice) and stressed mice treated with saline ( n = 15 cells; 8 mice) or ketamine ( n = 16 cells; 9 mice). Insets: histograms of the means obtained from sEPSC amplitude (left) or frequency (center). Right, example sEPSC traces. Scale bar, 100 ms, 20 pA. c , Left, AMPAR/NMDAR ratio in NAc D1-MSNs from stress-naïve mice ( n = 9 cells; 5 mice) and stressed mice who received saline ( n = 9 cells; 5 mice) or ketamine ( n = 8 cells; 4 mice) injections. Right, example traces for AMPAR/NMDAR ratio. Scale bars, 50 ms, 100 pA. e , Representative brain coronal section showing AAV10-ESYNDIO-HaloTagTM2A-dTomato transduction and cannula implantation track in the NAc from a D1-cre mouse. Scale bar, 100 µm. f , Sucrose preference in stressed ketamine-treated mice that received vehicle ( n = 7) or YM90K.1 -DART.1 ( n = 7) micro-injections in the NAc. g , Left, sociability index in stressed, ketamine-treated mice that received vehicle ( n = 7) or YM90K.1 -DART.1 ( n = 8) micro-injections in the NAc. Right, representative occupancy plots from stressed ketamine-treated mice who received vehicle or YM90K.1 -DART.1 micro-injections in the NAc. i , k , Performance during acquisition of the sucrose self-administration in stressed, ketamine-treated mice that received vehicle ( i , n = 6) or YM90K.1 -DART.1 in the NAc ( k , n = 7). j , l , Break points (left), total responses (center left), cumulative responses (center right), and slopes of cumulative responses (right) during the progressive ratio tests from stressed ketamine-treated mice that received vehicle or YM90K.1 -DART.1 micro-injections in the NAc. Data are mean ± s.e.m. ns, not significant. * P < 0.05, ** P < 0.01.

Article Snippet: For studies testing the necessity of specific inputs to the NAc in ketamine’s effect on motivated behavior, mice were injected with vehicle or CNO (10 mg/kg, Tocris) after PR2, and then 30 minutes later they were injected with ketamine.

Techniques: Saline, Transduction

Journal: bioRxiv

Article Title: Ketamine rescues anhedonia by cell-type and input specific adaptations in the Nucleus Accumbens

doi: 10.1101/2023.06.08.544088

Figure Lengend Snippet: a, Experimental timeline. b, Histograms of the means obtained from sEPSC amplitude (left) or frequencies (center) recorded from D2 cells in brain slices from stress-naïve mice ( n = 9 cells; 5 mice) and stressed mice that received saline ( n = 8 cells; 5 mice) or ketamine ( n = 6 cells; 4 mice). Right, example sEPSC traces. Scale bar, 100 ms, 10 pA. c, Left, AMPAR/NMDAR ratio in NAc D2-MSNs from stress-naïve mice ( n = 6 cells; 4 mice) and stressed mice that received saline ( n = 6 cells; 4 mice) or ketamine ( n = 6 cells; 4 mice). Right, example traces for AMPAR/NMDAR ratio. Scale bars, 100 ms, 50 pA. Data are mean ± s.e.m. ns, not significant.

Article Snippet: For studies testing the necessity of specific inputs to the NAc in ketamine’s effect on motivated behavior, mice were injected with vehicle or CNO (10 mg/kg, Tocris) after PR2, and then 30 minutes later they were injected with ketamine.

Techniques: Saline

Journal: bioRxiv

Article Title: Ketamine rescues anhedonia by cell-type and input specific adaptations in the Nucleus Accumbens

doi: 10.1101/2023.06.08.544088

Figure Lengend Snippet: a, Experimental timeline. b , Top, representative brain coronal sections showing AAV-CamKIIa-hChR2(H134R)-eyfp transduction in monosynaptic inputs to the NAc (mPFC, PVT, BLA and VH). Scale bar, 500 µm. Bottom, quantification of AMPAR/NMDAR ratio in NAc D1-MSNs evoked at mPFC, PVT, BLA and VH inputs from stress-naïve mice (mPFC: n = 8 cells, 5 mice; PVT: n = 10 cells, 5 mice; BLA: n = 10 cells, 6 mice; VH: n = 10 cells, 6 mice) and stressed mice that were treated with saline (mPFC: n = 10 cells, 6 mice; PVT: n = 11 cells, 5 mice; BLA: n = 9 cells, 6 mice; VH: n = 8 cells, 5 mice) or ketamine (mPFC: n = 9 cells, 6 mice; PVT: n = 11 cells, 5 mice; BLA: n = 11 cells, 6 mice; VH: n = 8 cells, 5 mice). Example traces for AMPAR/NMDAR ratio from each input. Scale bars, 100 ms, 100 pA. c , d , Top, light-evoked mPFC ( c ) and VH ( d ) qEPSCs at D1-MSNs recorded in the presence of strontium. Blue arrow indicates light pulse. Asterisks indicate qEPSCs. Scale bars, 100 ms, 20 pA. Insets: Overlay of individual (grey and black) and average (black and blue) onset-aligned qEPSCs from examples. Scale bars, 10 ms, 20 pA. Bottom, summary of the amplitude and frequency of mPFC ( c ) and VH ( d ) qEPSCs at D1-MSNs from stressed mice that received saline (mPFC: n = 6 cells, 4 mice; VH: n = 8 cells, 5 mice) or ketamine (mPFC: n = 9 cells, 5 mice; VH: n = 10 cells, 6 mice). Data are mean ± s.e.m. ns, not significant. * P < 0.05, ** P < 0.01, *** P < 0.001.

Article Snippet: For studies testing the necessity of specific inputs to the NAc in ketamine’s effect on motivated behavior, mice were injected with vehicle or CNO (10 mg/kg, Tocris) after PR2, and then 30 minutes later they were injected with ketamine.

Techniques: Transduction, Saline

Journal: bioRxiv

Article Title: Ketamine rescues anhedonia by cell-type and input specific adaptations in the Nucleus Accumbens

doi: 10.1101/2023.06.08.544088

Figure Lengend Snippet: a, d, Experimental timelines. b, c, Top left, representative brain coronal sections showing AAV-hSyn-DIO-HA-hM4D(Gi)-IRES-mcitrine transduction in mPFC ( b ) or VH ( c ) to NAc projecting neurons. Scale bar, 500 µm. Top right, sucrose preference of stressed mice that received vehicle or CNO injections before ketamine treatment in the mPFC ( b , vehicle: n = 9, CNO: n = 9) or VH ( c , vehicle: n = 8, CNO: n = 7) groups. Center, representative occupancy plots from stressed mice that received vehicle (right) or CNO (left) before ketamine treatment in the mPFC ( b ) or VH ( c ) groups. Bottom, sociability index, latency to first entry in the social chamber and social entries index in stressed mice who received vehicle or CNO injections before ketamine treatment in the mPFC ( b , vehicle: n = 11, CNO: n = 13) or VH ( c , vehicle: n = 9, CNO: n = 7) groups. e, f, Break points (left), total responses (center left), cumulative responses (center), slopes of cumulative responses (center right), and latency to first nose-poke (right) during the progressive ratio tests from stressed mice that received vehicle or CNO injections before ketamine treatment in the mPFC ( g , vehicle: n = 12, CNO: n = 15) or VH ( h, vehicle: n = 11, CNO: n = 10) groups. Data are mean ± s.e.m. ns, not significant. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001.

Article Snippet: For studies testing the necessity of specific inputs to the NAc in ketamine’s effect on motivated behavior, mice were injected with vehicle or CNO (10 mg/kg, Tocris) after PR2, and then 30 minutes later they were injected with ketamine.

Techniques: Transduction

Journal: bioRxiv

Article Title: Ketamine rescues anhedonia by cell-type and input specific adaptations in the Nucleus Accumbens

doi: 10.1101/2023.06.08.544088

Figure Lengend Snippet: a, b, Left, Schematic of the experiment. Right, resting membrane potential (RMP) and action potential (AP) frequency evoked by somatic depolarizing current steps before and after bath application of CNO (10 uM) from mPFC-( a, n = 4 cells; 2 mice) or VH-( b, n = 7 cells; 3 mice) NAc projecting pyramidal neurons. Scale bar, 100 ms, 10 mV. c , d , Mapping showing the expression of AAV-hSyn-DIO-HA-hM4D(Gi)-IRES-mcitrine in mPFC ( c ) or VH ( d ). e , Experimental timeline. f , Sucrose preference (left) and sociability index (center) in stressed mice that received CNO injections before saline ( n = 6) or ketamine ( n = 6) treatment. Right, representative occupancy plots from stressed mice that received CNO injections before saline or ketamine treatment. Data are mean ± s.e.m. * P < 0.05, ** P < 0.01.

Article Snippet: For studies testing the necessity of specific inputs to the NAc in ketamine’s effect on motivated behavior, mice were injected with vehicle or CNO (10 mg/kg, Tocris) after PR2, and then 30 minutes later they were injected with ketamine.

Techniques: Membrane, Expressing, Saline