Rapid versus Delayed Stimulation of Feeding by the Endogenously Released AgRP Neuron Mediators GABA, NPY, and AgRP  Michael J. Krashes, Bhavik P. Shah,

Slides:



Advertisements
Similar presentations
Volume 10, Issue 4, Pages (October 2009)
Advertisements

Volume 123, Issue 3, Pages (November 2005)
Volume 20, Issue 6, Pages (December 2014)
Parabrachial CGRP Neurons Control Meal Termination
Volume 26, Issue 17, Pages (September 2016)
Volume 20, Issue 2, Pages (August 2014)
Liang Yang, Yong Qi, Yunlei Yang  Cell Reports 
Volume 17, Issue 7, Pages (November 2016)
Volume 71, Issue 1, Pages (July 2011)
Sensory Detection of Food Rapidly Modulates Arcuate Feeding Circuits
Volume 14, Issue 3, Pages (September 2011)
Applying the Brakes: When to Stop Eating
Volume 4, Issue 3, Pages (September 2006)
Volume 12, Issue 1, Pages (July 2010)
Volume 59, Issue 6, Pages (September 2008)
Volume 27, Issue 16, Pages e3 (August 2017)
Volume 18, Issue 6, Pages (December 2013)
Volume 17, Issue 7, Pages (November 2016)
Volume 51, Issue 6, Pages (September 2006)
Volume 89, Issue 5, Pages (March 2016)
High Plasticity of New Granule Cells in the Aging Hippocampus
Volume 90, Issue 5, Pages (June 2016)
Volume 2, Issue 6, Pages (December 2005)
Diet-Induced Obese Mice Retain Endogenous Leptin Action
Volume 93, Issue 1, Pages (January 2017)
Volume 13, Issue 4, Pages (April 2011)
Critical Role for Hypothalamic mTOR Activity in Energy Balance
Volume 90, Issue 6, Pages (June 2016)
Heparin Increases Food Intake through AgRP Neurons
Volume 10, Issue 2, Pages (August 2009)
Volume 13, Issue 2, Pages (February 2011)
Ryan G. Natan, Winnie Rao, Maria N. Geffen  Cell Reports 
Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors
Volume 21, Issue 4, Pages (October 2017)
Volume 90, Issue 6, Pages (June 2016)
Volume 15, Issue 5, Pages (May 2012)
Volume 49, Issue 2, Pages (January 2006)
Volume 6, Issue 5, Pages (November 2007)
Input-Timing-Dependent Plasticity in the Hippocampal CA2 Region and Its Potential Role in Social Memory  Felix Leroy, David H. Brann, Torcato Meira, Steven.
Volume 21, Issue 11, Pages (December 2017)
TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons
Volume 23, Issue 6, Pages (June 2016)
Han Xu, Hyo-Young Jeong, Robin Tremblay, Bernardo Rudy  Neuron 
Volume 9, Issue 6, Pages (June 2009)
Volume 24, Issue 1, Pages (September 1999)
Volume 73, Issue 3, Pages (February 2012)
Volume 87, Issue 6, Pages (September 2015)
Volume 4, Issue 4, Pages (October 2006)
Volume 5, Issue 1, Pages (January 2007)
Cell-Type Specificity of Callosally Evoked Excitation and Feedforward Inhibition in the Prefrontal Cortex  Paul G. Anastasiades, Joseph J. Marlin, Adam.
Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice  Decheng Ren, Minghua Li, Chaojun Duan, Liangyou.
Karen M. Crosby, Wataru Inoue, Quentin J. Pittman, Jaideep S. Bains 
Treating obesity: Does antagonism of NPY fit the bill?
Volume 5, Issue 6, Pages (June 2007)
Volume 23, Issue 6, Pages (June 2016)
Antagonistic but Not Symmetric Regulation of Primary Motor Cortex by Basal Ganglia Direct and Indirect Pathways  Ian A. Oldenburg, Bernardo L. Sabatini 
Volume 7, Issue 3, Pages (March 2008)
Volume 22, Issue 6, Pages (December 2015)
Volume 91, Issue 1, Pages (July 2016)
Sorting Nexin 27 Regulation of G Protein-Gated Inwardly Rectifying K+ Channels Attenuates In Vivo Cocaine Response  Michaelanne B. Munoz, Paul A. Slesinger 
Volume 1, Issue 6, Pages (June 2005)
AgRP in energy balance: Will the real AgRP please stand up?
Volume 10, Issue 6, Pages (December 2009)
Volume 28, Issue 23, Pages e3 (December 2018)
Volume 5, Issue 1, Pages (January 2007)
Clemence Blouet, Gary J. Schwartz  Cell Metabolism 
Activation of LHAGABA neurons increases motivated feeding and chow intake. Activation of LHAGABA neurons increases motivated feeding and chow intake. A,
Volume 5, Issue 3, Pages (March 2007)
Volume 20, Issue 4, Pages (October 2014)
Gwendolyn G. Calhoon, Patricio O’Donnell  Neuron 
Presentation transcript:

Rapid versus Delayed Stimulation of Feeding by the Endogenously Released AgRP Neuron Mediators GABA, NPY, and AgRP  Michael J. Krashes, Bhavik P. Shah, Shuichi Koda, Bradford B. Lowell  Cell Metabolism  Volume 18, Issue 4, Pages 588-595 (October 2013) DOI: 10.1016/j.cmet.2013.09.009 Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 1 Acute Pharmacogenetic Activation of AgRP Neurons in Mice without the Release of GABA, NPY, and AgRP Signaling via MC4Rs, Collectively, Lack DREADD-Mediated Increases in Food Intake Data were pooled across multiple trials. All mice in these studies were bilaterally injected with AAV8-DIO-hM3Dq-mCherry in the ARC. (A and B) The activation of AgRP neurons increases food intake in AgRP-ires-Cre mice (black line) but has no effect on food intake in AgRP-ires-Cre; Mc4r−/−; Vgatflox/flox; Npy−/− triple KO mice (light green line). CNO (solid line; 0.3 mg/kg of body weight, i.p.) or saline (dotted line) was injected 3 hr after the start of the lights on cycle, and food intake was assessed 1 and 2 (A) and 4, 8, and 24 hr (B) postinjection (PI) over three trials of each treatment. Data shown are from male mice (error bars indicate mean ± SEM, n = 8 AgRP-ires-Cre mice; n = 5 AgRP-ires-Cre; Mc4r−/−; Vgatflox/flox; Npy−/− mice; ∗p < 0.05 AgRP-ires-Cre CNO group versus all other groups; #p < 0.05 AgRP-ires-Cre; Mc4r−/−; Vgatflox/flox; Npy−/− groups versus AgRP-ires-Cre saline group). (C) Immunohistochemical analysis of AgRP projections in AgRP-ires-Cre mice (left) and AgRP-ires-Cre; Mc4r−/−; Vgatflox/flox; Npy−/− triple KO mice (right) to (top-bottom) the bed nucleus of the stria terminalis (BST), paraventricular hypothalamus (PVH), paraventricular thalamus (PVT), and lateral parabrachial nucleus (PBNl) reveals no gross differences in morphology and/or density (200 μm). See also Figures S1 and S4 and Table S1. Cell Metabolism 2013 18, 588-595DOI: (10.1016/j.cmet.2013.09.009) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 2 Acute Pharmacogenetic Activation of AgRP Neurons in Mice without the Release of GABA, NPY, or AgRP Signaling via MC4Rs, Individually, Display Intact DREADD-Mediated Increases in Food Intake Data were pooled across multiple trials. All mice in these studies were bilaterally injected with AAV8-DIO-hM3Dq-mCherry in the ARC. (A–C) The activation of AgRP neurons increases comparable levels of food intake and latency to first meal in AgRP-ires-Cre mice (black line), AgRP-ires-Cre; Mc4r−/− KO mice (gray line), AgRP-ires-Cre; Vgatflox/flox KO mice (red line), and AgRP-ires-Cre; Npy−/− KO mice (blue line). CNO (solid line; 0.3 mg/kg of body weight, i.p.) or saline (dotted line) was injected 3 hr after the start of the lights on cycle, and food intake was assessed 1 and 2 (A) and 4, 8, and 24 hr (B) PI over three trials of each treatment. Data shown are from male mice (Error bars indicate mean ± SEM, n = 8 AgRP-ires-Cre mice; n = 5 AgRP-ires-Cre; Mc4r−/− mice; n = 7 AgRP-ires-Cre; Vgatflox/flox mice; n = 8 AgRP-ires-Cre; Npy−/− mice; ∗p < 0.05 CNO groups versus all saline groups; #p < 0.05 AgRP-ires-Cre; Mc4r−/− saline group versus all other saline groups). (C) Latency to first meal after acute pharmacogenetic activation of AgRP neurons. Each circle represents the average of two trials for each mouse; the horizontal bar represents the average of all mice. Data shown are from male mice (mean ± SEM, n = 7 AgRP-ires-Cre mice; n = 5 AgRP-ires-Cre; Mc4r−/− mice; n = 5 AgRP-ires-Cre; Vgatflox/flox mice; n = 5 AgRP-ires-Cre; Npy−/− KO mice). See also Figure S2 and Table S1. Cell Metabolism 2013 18, 588-595DOI: (10.1016/j.cmet.2013.09.009) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 3 Acute Pharmacogenetic Activation of AgRP Neurons in Mice without the Release of GABA and NPY, collectively, Display Delayed DREADD-Mediated Increases in Food Intake Data were pooled across multiple trials. All mice in these studies were bilaterally injected with AAV8-DIO-hM3Dq-mCherry in the ARC. (A–C) The activation of AgRP neurons increases comparable levels of food intake (A and B) and latency to first meal (C) in AgRP-ires-Cre mice (black line), AgRP-ires-Cre; Mc4r−/−; Vgatflox/flox double KO mice (orange line), and AgRP-ires-Cre; Mc4r−/−; Npy−/− double KO mice (green line). In contrast, the activation of AgRP neurons in AgRP-ires-Cre; Vgatflox/flox; Npy−/− double KO mice (purple line) resulted in highly attenuated short-term feeding (A), increased latency to first meal (C), and late-onset hyperphagia (B). CNO (solid line; 0.3 mg/kg of body weight, i.p.) or saline (dotted line) was injected 3 hr after the start of the lights on cycle and food intake was assessed 1 and 2 (A) and 4, 8, and 24 hr (B) PI over three trials of each treatment. Data shown are from male mice (error bars indicate mean ± SEM, n = 8 AgRP-ires-Cre mice; n = 5 AgRP-ires-Cre; Mc4r−/−; Vgatflox/flox mice; n = 5 AgRP-ires-Cre; Mc4r−/−; Npy−/− mice; n = 8 AgRP-ires-Cre; Vgatflox/flox; Npy−/− mice; ∗p < 0.05 AgRP-ires-Cre, AgRP-ires-Cre; Mc4r−/−; Vgatflox/flox and AgRP-ires-Cre; Mc4r−/−; Npy−/− CNO groups versus AgRP-ires-Cre; Vgatflox/flox; Npy−/− CNO and all saline groups; #p < 0.05 AgRP-ires-Cre; Mc4r−/−; Vgatflox/flox and AgRP-ires-Cre; Mc4r−/−; Npy−/− saline groups versus all other saline groups; &p < 0.05 AgRP-ires-Cre; Vgatflox/flox; Npy−/− CNO group versus all saline groups). (C) Latency to first meal after acute pharmacogenetic activation of AgRP neurons. Each circle represents the average of two trials for each mouse; the horizontal bar represents the average of all mice. Data shown are from male mice (mean ± SEM, n = 7 AgRP-ires-Cre mice; n = 5 AgRP-ires-Cre; Mc4r−/−; Vgatflox/flox mice; n = 5 AgRP-ires-Cre; Mc4r−/−; Npy−/− mice; n = 5 AgRP-ires-Cre; Vgatflox/flox; Npy−/− mice; ∗p < 0.05 AgRP-ires-Cre; Vgatflox/flox; Npy−/− group versus all other groups). See also Figure S3 and Table S1. Cell Metabolism 2013 18, 588-595DOI: (10.1016/j.cmet.2013.09.009) Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 4 Mice with the Compromised Release of Both GABA and NPY from AgRP Neurons Display a Delayed Physiological Increase in Dark Cycle Food Intake (A) Light cycle (10 a.m.; n = 8) versus dark cycle (10 p.m.; n = 9) electrophysiological properties of AgRP neurons (error bars indicate mean + SEM; ∗p < 0.05). Top, representative trace of AgRP neuron in the light cycle. Bottom, representative trace of AgRP neuron in the dark cycle. Right, quantitative analyses of firing rate and membrane potential of AgRP neurons in the light cycle (black bar) versus dark cycle (white bar). (B and C) Dark cycle food intake measurements assessed at 2 and 4 (B) and 12 and 24 hr (C) after lights are shut off. Grey background indicates the dark cycle period. Data shown are from male mice (error bars indicate mean ± SEM, n = 9 AgRP-ires-Cre mice; n = 9 AgRP-ires-Cre; Vgatflox/flox; Npy−/− mice; ∗p < 0.05). Cell Metabolism 2013 18, 588-595DOI: (10.1016/j.cmet.2013.09.009) Copyright © 2013 Elsevier Inc. Terms and Conditions