Daniel Philipp Holschneider, MD

My laboratory’s primary interest over the past 15 years has been the brain imaging of rodent behaviors as they occur in the nontethered, nonrestrained animal. A primary tool has been perfusion based mapping using the classic autoradiographic methods. Unique about our methods is that they allow us to evaluate changes in functional brain activation at the circuit level across the entire brain. Perfusion or metabolic mapping, as we have proposed, fills a gap in the current armamentarium of imaging tools in that it can deliver a 3D assessment of functional activation of the awake, nonrestrained animal, with a spatial resolution of 100 microns.
We have made significant contributions to the methodology in several areas (a) adapting statistical parametric mapping and connectivity analyses to three-dimensional autoradiographic data sets of the rat and mouse brain, (b) developing methods to allow the generation of cortical flat maps in rats and, (c) developing an implantable minipump that allows radiotracer bolus administration by remote activation in the freely moving animal. An ongoing focus is the application of functional connectivity analyses [correlation matrices of regional changes in CBF, graph theoretical analysis of network �hubs� (Pajek software), effective connectivity analyses using structural equation modeling].
The lab has broad experience evaluating behavioral function in rat and mouse models of pain, brain injury, and fear, as well as exercise. Extensive experience is available for vascular surgical procedures in rats, mice and rabbits, as well as expertise in physiologic monitoring (locomotor activity, telemetric monitoring of EMG, EEG, ECG, cardiac output).

The expertise of the laboratory include functional brain mapping, animal behavior, physiologic monitoring (EEG, EMG, EKG) and basic histochemistry.

• Increased perivascular space volume in white matter and basal ganglia is associated with cognition in Parkinson’s Disease Brain Imaging Behav. 2024 Feb; 18(1):57-65. . View in PubMed
• Exercise alters cortico-basal ganglia network metabolic connectivity: a mesoscopic level analysis informed by anatomic parcellation defined in the mouse brain connectome Brain Struct Funct. 2023 Nov; 228(8):1865-1884. . View in PubMed
• Physical activity intensity is associated with cognition and functional connectivity in Parkinson’s disease Parkinsonism Relat Disord. 2022 Nov; 104:7-14. . View in PubMed
• A gut-derived metabolite alters brain activity and anxiety behaviour in mice Nature. 2022 02; 602(7898):647-653. . View in PubMed
• A mind in motion: Exercise improves cognitive flexibility, impulsivity and alters dopamine receptor gene expression in a Parkinsonian rat model Curr Res Neurobiol. 2022; 3:100039. . View in PubMed
• Thalamic volume mediates associations between cardiorespiratory fitness (VO2max) and cognition in Parkinson’s disease Parkinsonism Relat Disord. 2021 05; 86:19-26. . View in PubMed
• The Effects of Cardiorespiratory and Motor Skill Fitness on Intrinsic Functional Connectivity of Neural Networks in Individuals with Parkinson’s Disease Brain Plast. 2021; 7(2):77-95. . View in PubMed
• Ceftriaxone inhibits stress-induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study Neurourol Urodyn. 2020 08; 39(6):1628-1643. . View in PubMed
• Voluntary exercise improves voiding function and bladder hyperalgesia in an animal model of stress-induced visceral hypersensitivity: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study Neurourol Urodyn. 2020 02; 39(2):603-612. . View in PubMed
• Modulation of Hippocampal GABAergic Neurotransmission and Gephyrin Levels by Dihydromyricetin Improves Anxiety Front Pharmacol. 2020; 11:1008. . View in PubMed
• Exercise modulates neuronal activation in the micturition circuit of chronically stressed rats: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study Physiol Behav. 2020 03 01; 215:112796. . View in PubMed
• Cognitive flexibility deficits in rats with dorsomedial striatal 6-hydroxydopamine lesions tested using a three-choice serial reaction time task with reversal learning Neuroreport. 2020 10 14; 31(15):1055-1064. . View in PubMed
• Positive Allosteric Modulation of Cholinergic Receptors Improves Spatial Learning after Cortical Contusion Injury in Mice J Neurotrauma. 2019 07 15; 36(14):2233-2245. . View in PubMed
• Cerebral perfusion mapping during retrieval of spatial memory in rats Behav Brain Res. 2019 12 16; 375:112116. . View in PubMed
• Hypothalamus-hippocampus circuitry regulates impulsivity via melanin-concentrating hormone Nat Commun. 2019 10 29; 10(1):4923. . View in PubMed
• Sex differences in insular functional connectivity in response to noxious visceral stimulation in rats Brain Res. 2019 08 15; 1717:15-26. . View in PubMed
• Recruitment of prefrontal-striatal circuit in response to skilled motor challenge Neuroreport. 2017 Dec 13; 28(18):1187-1194. . View in PubMed
• Measurement of Cardiac Output and Blood Volume During Hemodialysis with Fluorescent Dye Dilution Technique Ann Biomed Eng. 2017 03; 45(3):580-591. . View in PubMed
• Effects of water avoidance stress on peripheral and central responses during bladder filling in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study PLoS One. 2017; 12(9):e0182976. . View in PubMed
• Engaging cognitive circuits to promote motor recovery in degenerative disordersexercise as a learning modality. J Hum Kinet. 2016 Sep 01; 52:35-51. . View in PubMed
• Early life stress elicits visceral hyperalgesia and functional reorganization of pain circuits in adult rats Neurobiol Stress. 2016 Jun 01; 3:8-22. . View in PubMed
• Evidence of functional brain reorganization on the basis of blood flow changes in the CAG140 knock-in mouse model of Huntington’s disease Neuroreport. 2016 06 15; 27(9):632-9. . View in PubMed
• Prone positioning decreases cardiac output and increases systemic vascular resistance in neonates J Perinatol. 2015 Jun; 35(6):424-7. . View in PubMed
• Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise Neurobiol Dis. 2015 May; 77:71-87. . View in PubMed
• Neonatal stress from limited bedding elicits visceral hyperalgesia in adult rats Neuroreport. 2015 Jan 07; 26(1):13-6. . View in PubMed
• Exercise alters resting-state functional connectivity of motor circuits in parkinsonian rats Neurobiol Aging. 2015 Jan; 36(1):536-44. . View in PubMed
• The Effects of Exercise on Dopamine Neurotransmission in Parkinson’s Disease: Targeting Neuroplasticity to Modulate Basal Ganglia Circuitry Brain Plast. 2015; 1(1):29-39. . View in PubMed
• Exercise training reinstates cortico-cortical sensorimotor functional connectivity following striatal lesioning: development and application of a subregional-level analytic toolbox for perfusion autoradiographs of the rat brain Front Phys. 2014 Dec 03; 2. . View in PubMed
• Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study Front Neuroinform. 2014; 8:61. . View in PubMed
• Remote brain network changes after unilateral cortical impact injury and their modulation by acetylcholinesterase inhibition J Neurotrauma. 2013 Jun 01; 30(11):907-19. . View in PubMed
• Functional reorganization of motor and limbic circuits after exercise training in a rat model of bilateral parkinsonism PLoS One. 2013; 8(11):e80058. . View in PubMed
• Alterations in prefrontal-limbic functional activation and connectivity in chronic stress-induced visceral hyperalgesia PLoS One. 2013; 8(3):e59138. . View in PubMed
• Acetylcholinesterase inhibition interacts with training to reverse spatial learning deficits after cortical impact injury J Neurotrauma. 2012 Oct 10; 29(15):2457-64. . View in PubMed
• Circadian rhythmicity in serotonin transporter knockout mice Life Sci. 2012 Oct 05; 91(11-12):365-368. . View in PubMed
• Ceftriaxone upregulates the glutamate transporter in medial prefrontal cortex and blocks reinstatement of methamphetamine seeking in a condition place preference paradigm Brain Res. 2012 May 25; 1456:14-21. . View in PubMed
• Anxiolytic-like effect of pregabalin on unconditioned fear in the rat: an autoradiographic brain perfusion mapping and functional connectivity study Neuroimage. 2012 Feb 15; 59(4):4168-88. . View in PubMed
• Functional brain activation during retrieval of visceral pain-conditioned passive avoidance in the rat Pain. 2011 Dec; 152(12):2746-2756. . View in PubMed
• Acetylcholinesterase inhibition and locomotor function after motor-sensory cortex impact injury J Neurotrauma. 2011 Sep; 28(9):1909-19. . View in PubMed
• Antenatal maternal stress alters functional brain responses in adult offspring during conditioned fear Brain Res. 2011 Apr 18; 1385:163-74. . View in PubMed
• The role of exercise in facilitating basal ganglia function in Parkinson’s disease Neurodegener Dis Manag. 2011 Apr 01; 1(2):157-170. . View in PubMed
• The role of experimental models in developing new treatments for irritable bowel syndrome Expert Rev Gastroenterol Hepatol. 2011 Feb; 5(1):43-57. . View in PubMed
• Mapping functional brain activation using [14C]-iodoantipyrine in male serotonin transporter knockout mice PLoS One. 2011; 6(8):e23869. . View in PubMed
• Powering an implantable minipump with a multi-layered printed circuit coil for drug infusion applications in rodents Ann Biomed Eng. 2010 Mar; 38(3):707-13. . View in PubMed
• A low power, on demand electrothermal valve for wireless drug delivery applications Lab Chip. 2010 Jan 07; 10(1):101-10. . View in PubMed
• Enhancing neuroplasticity in the basal ganglia: the role of exercise in Parkinson’s disease Mov Disord. 2010; 25 Suppl 1:S141-5. . View in PubMed
• A Parylene MEMS Electrothermal Valve J Microelectromech Syst. 2009 Dec; 18(6):1184-1197. . View in PubMed
• Sex differences in functional brain activation during noxious visceral stimulation in rats Pain. 2009 Sep; 145(1-2):120-128. . View in PubMed
• Estimation of indocyanine green concentration in blood from fluorescence emission: application to hemodynamic assessment during hemodialysis J Biomed Opt. 2009 Sep-Oct; 14(5):054006. . View in PubMed
• Snap-frozen brain tissue sections stored with desiccant at ambient laboratory conditions without chemical fixation are resistant to degradation for a minimum of 6 months Appl Immunohistochem Mol Morphol. 2009 Mar; 17(2):165-71. . View in PubMed
• Studying the brain-gut axis with pharmacological imaging Ann N Y Acad Sci. 2008 Nov; 1144:256-64. . View in PubMed
• Memory, mood, dopamine, and serotonin in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of basal ganglia injury Neurobiol Dis. 2008 Nov; 32(2):319-27. . View in PubMed
• Changes in regional brain perfusion during functional brain activation: comparison of [(64)Cu]-PTSM with [(14)C]-Iodoantipyrine Brain Res. 2008 Oct 09; 1234:32-43. . View in PubMed
• Regional brain activation in conscious, nonrestrained rats in response to noxious visceral stimulation Pain. 2008 Aug 15; 138(1):233-243. . View in PubMed
• Brain maps on the go: functional imaging during motor challenge in animals Methods. 2008 Aug; 45(4):255-61. . View in PubMed
• Flattened cortical maps of cerebral function in the rat: a region-of-interest approach to data sampling, analysis and display Neurosci Lett. 2008 Mar 28; 434(2):179-84. . View in PubMed
• Reorganization of functional brain maps after exercise training: Importance of cerebellar-thalamic-cortical pathway Brain Res. 2007 Dec 12; 1184:96-107. . View in PubMed
• Changes in brain functional activation during resting and locomotor states after unilateral nigrostriatal damage in rats Neuroimage. 2007 Jul 01; 36(3):755-73. . View in PubMed
• Fluorescence dilution technique for measurement of cardiac output and circulating blood volume in healthy human subjects Anesthesiology. 2007 Mar; 106(3):491-8. . View in PubMed
• Transcutaneous RF-powered implantable minipump driven by a class-E transmitter IEEE Trans Biomed Eng. 2006 Aug; 53(8):1705-8. . View in PubMed
• Mapping cerebral blood flow changes during auditory-cued conditioned fear in the nontethered, nonrestrained rat Neuroimage. 2006 Feb 15; 29(4):1344-58. . View in PubMed
• In vivo quantitative assessment of catheter patency in rats Lab Anim. 2005 Jul; 39(3):259-68. . View in PubMed
• Transcutaneous fluorescence dilution cardiac output and circulating blood volume during hemorrhagic hypovolemia Anesthesiology. 2005 Apr; 102(4):774-82. . View in PubMed
• A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior J Biol Chem. 2004 Sep 17; 279(38):39645-52. . View in PubMed
• Mapping brain function in freely moving subjects Neurosci Biobehav Rev. 2004 Sep; 28(5):449-61. . View in PubMed
• Statistical parametric mapping applied to an autoradiographic study of cerebral activation during treadmill walking in rats Neuroimage. 2004 Sep; 23(1):252-9. . View in PubMed
• Measurement of cardiac output with indocyanine green transcutaneous fluorescence dilution technique Anesthesiology. 2004 Jun; 100(6):1476-83. . View in PubMed
• Striatal damage and oxidative stress induced by the mitochondrial toxin malonate are reduced in clorgyline-treated rats and MAO-A deficient mice Neurochem Res. 2004 Apr; 29(4):741-6. . View in PubMed
• Activation of cerebral cortex during acoustic challenge or acute foot-shock in freely moving, nontethered rats Neurosci Lett. 2004 Jan 02; 354(1):74-8. . View in PubMed
• Functional brain mapping in freely moving rats during treadmill walking J Cereb Blood Flow Metab. 2003 Aug; 23(8):925-32. . View in PubMed
• An implantable bolus infusion pump for use in freely moving, nontethered rats Am J Physiol Heart Circ Physiol. 2002 Oct; 283(4):H1713-9. . View in PubMed
• Fluorescence of indocyanine green in blood: intensity dependence on concentration and stabilization with sodium polyaspartate J Photochem Photobiol B. 2001 Dec 31; 65(2-3):157-64. . View in PubMed
• Biochemical, behavioral, physiologic, and neurodevelopmental changes in mice deficient in monoamine oxidase A or B Brain Res Bull. 2001 Nov 15; 56(5):453-62. . View in PubMed
• Genotype to phenotype: challenges and opportunities Int J Dev Neurosci. 2000 Oct; 18(6):615-8. . View in PubMed
• Attenuation of brain high frequency electrocortical response after thiopental in early stages of Alzheimer’s dementia Psychopharmacology (Berl). 2000 Mar; 149(1):6-11. . View in PubMed
• Regional cerebral cortical activation in monoamine oxidase A-deficient mice: differential effects of chronic versus acute elevations in serotonin and norepinephrine Neuroscience. 2000; 101(4):869-77. . View in PubMed
• Changes in electrocortical power and coherence in response to the selective cholinergic immunotoxin 192 IgG-saporin Exp Brain Res. 1999 May; 126(2):270-80. . View in PubMed
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• Selective immunotoxin-induced cholinergic deafferentation alters blood flow distribution in the cerebral cortex Brain Res. 1999 Feb 06; 818(1):1-11. . View in PubMed
• Lack of protection from ischemic injury of monoamine oxidase B-deficient mice following middle cerebral artery occlusion Neurosci Lett. 1999 Jan 15; 259(3):161-4. . View in PubMed
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• Clinical neurophysiology using electroencephalography in geriatric psychiatry: neurobiologic implications and clinical utility J Geriatr Psychiatry Neurol. 1999; 12(3):150-64. . View in PubMed
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• Changes in cortical EEG and cholinergic function in response to NGF in rats with nucleus basalis lesions Brain Res. 1997 Aug 15; 765(2):228-37. . View in PubMed
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• Toga, Arthur
• Thompson, Paul
• Shih, Jean
• Peterson, Bradley
• Wang, Danny