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Dr. Manuel Diaz

Dr. Diaz Laboratory

About Us:

We have federal funded projects focused on assessing the role of sensory feedback (sensory information) coming from our lower limbs via peripheral nerves onto networks (groups) of cells located in our spinal cord after a spinal cord injury (SCI). We also have projects studying the role of spinal networks and its component neurons in the control of locomotion and its changes due to the use of neuromodulatory substances such as caffeine, ethanol, taurine, and others.

To perform the experiments which are relevant to the projects described above, we use electrophysiological techniques, such as intracellular whole-cell patch clamp recordings and extracellular nerve recordings, confocal imaging, and immunohistochemistry.

Our research and mentoring objectives:

1) Neuromodulation of cellular networks

The effects of that neural chemicals known as neurotransmitters or neuropeptides can have on basic mechanisms that occur in our central nervous system is well documented and is known to be very significant. The consumption of known natural or artificial psychostimulants, such as caffeine, by animals or humans can have a significant impact on the short and long-term performance of cognitive and/or motor skills. These results support the stimulant effects of caffeine onto adenosine receptors located within the spinal network controlling walking, acting mostly through the inhibition of A1 adenosine receptors. We want to understand the cellular mechanisms by which adenosine receptor antagonists and agonist modulates the firing properties of the spinal CPG network for locomotion since adenosine receptors have been related to the reduction of inflammation and neuroprotection after a spinal cord injury.

2) Identification of the segmental neural circuits controlling trunk motor coordination

Trunk motor control is crucial after a spinal cord injury (SCI) for both animals and humans. Several rehabilitative strategies are aimed at enhancing trunk stabilization and postural control after an SCI. It has been recently shown that SCI rats that can still support weight show increased compression and stiffening of the trunk as a compensating mechanism to improve overall motor activity patterns during standing and walking. Additionally, effective robot rehabilitation training on adult rats spinally transected as neonates has shown significant reorganization of the trunk motor cortex to be induced and a partial reversal of some plastic changes that may be adaptive in non-stepping paraplegia after SCI. Trunk stabilization has also been proven to be essential for numerous wheel chair activities and for postural control and propulsion during assisted locomotion in human SCI patients. Thus the study of the thoracic neural network involved in trunk stabilization and postural control will refine current therapeutic strategies for treating SCI patients by including the reacquisition of trunk-related motor activity as part of the rehabilitation process.

3) Mentoring impact

These studies expose students from underrepresented groups in science (including hispanics and women) to advanced instrumentation and experimental techniques. Furthering the scientific career of underrepresented groups in science is of high priority in our research laboratory and aligned to the programmatic mission of federal organizations such as the National Institute of Health (NIH) and the National Science Foundation (NSF).

 

Laboratory Personnel

Laboratory Administrator:

  • Mildred Camacho, B.S.

Post-Doctoral Associate:

  • Garrett Seale, Ph.D.
Post-Doctoral Research Associate
Brown University, B.S. (Neuroscience)
Columbia University, Ph.D. (Neurobiology & Behavior)
 
Graduate Students:
  • Marla S. Rivera-Oliver, B.S.
Doctoral Candidate
Biology – Neuroscience Track
Univ. of Puerto Rico, Rio Piedras Campus
  • Ernesto Cabezas-Bou, B.S.
Graduate Student
Biology – Neuroscience Track
Univ. of Puerto Rico, Rio Piedras Campus
  • Yocasta Alvarez-Bagnarol, B.S.
MD/PhD Student
Univ. of Puerto Rico, Medical Sciences Campus
 
Undergraduate Students:
 
  • Lauren Rivera-Pagan
Cellular and Molecular Biology
Univ. of Puerto Rico, Rio Piedras Campus
  • Christian Ayala
Cellular and Molecular Biology
Univ. of Puerto Rico, Rio Piedras Campus
  • Ariana Saadipour-Selles
Cellular and Molecular Biology
Univ. of Puerto Rico, Rio Piedras Campus
 
Former Students:
 
  • Jean M. Acevedo, Ph.D.
Univ. of Puerto Rico, Medical Sciences Campus (Anatomy & Neurobiology)
  • Nikol Matos-Vergara, M.S. Student
Psychology
Interamerican Univ. of Puerto Rico, Metro Campus
  • Alexandra Santana, B.S.
MD Student
Univ. of Puerto Rico, Medical Sciences Campus
 
Collaborators:
 
Shawn Hochman, Ph.D.
Dept. of Physiology
Emory Univ. School of Medicine
 
Marie-Claude Perreault, Ph.D.
Dept. of Physiology
Emory Univ. School of Medicine
 
Alex Kwan, Ph.D.
Dept. of Psychiatry
Yale School of Medicine
 
Thomas Cleland, Ph.D.
Dept. of Psychology
Cornell University
 
Nelson Cruz, Ph.D.
Dept. of Psychology
Univ. of Puerto Rico, Rio Piedras Campus
 
Dr. Karla Narvaez
Clinical Psychologist 
Private Practice
 
Jorge Miranda, Ph.D.
Dept. of Physiology
Univ. of Puerto Rico, Medical Sciences Campus
 
Andreas Husch, Ph.D.
Institute of Genetics
University of Bonn, Germany
 
Sergi Ferre, M.D.,Ph.D. Senior Investigator
Chief, Integrative Neurobiology Section
National Institute of Drug Abuse- Intramural Research
 
Dr. Vicent Casado, Ph.D. 
Dept. of Biochemistry and Molecular Biology
University of Barcelona, Spain

 

Laboratory Publications

Acevedo J, Santana-Almansa A, Matos-Vergara N, Marrero-Cordero LR, Cabezas-Bou E, Díaz-Ríos M. Caffeine stimulates locomotor activity in the mammalian spinal cord via adenosine A1 receptor-dopamine D1 receptor interaction and PKA-dependent mechanisms. Neuropharmacology. (2015) 101:490-505 doi: 10.1016/j.neuropharm.2015.10.020. 
 
River-Oliver M, Diaz-Rios M. Using caffeine and other adenosine receptor antagonists and agonist as therapeutic tools against neurodegenerative diseases: a review.  Life Sci. (2014) 101(1-2):1-9. doi: 10.1016/j.lfs.2014.01.083.
 
Acevedo JM, Diaz-Rios M. Removing sensory input disrupts spinal locomotor activity in the early postnatal period. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. (2013) 199(12):1105-16. doi: 10.1007/s00359-013-0853-3.

Díaz-Ríos M., Dombeck D., Webb W.W., and Harris-Warrick R. M. Serotonin modulates dendritic calcium influx in commissural interneurons in the mouse spinal locomotor network. (2007) J Neurophysiol  98(4):2157-67.

Wilson J., Dombeck D., Díaz-Ríos M., Harris-Warrick R.M., and Brownstone R.M.  Two-photon calcium imaging of network activity in XFP expressing neurons in the mouse. (2007) J Neurophysiol. 97(4):3118-25.

Zhong G., Díaz-Ríos M., and Harris-Warrick R.M. Intrinsic and functional differences among commissural interneurons in the central pattern generator for locomotion in the neonatal mouse. (2006) J Neurosci. 26(24):6509-17.

Díaz-Ríos M., and Miller M.W. Target-specific regulation of synaptic efficacy in the feeding central pattern generator of Aplysia:  Potential substrates for behavioral plasticity? (2006) Biol Bull. 210(3):215-29.

Zhong G., Díaz-Ríos M. and Harris-Warrick R.M.  Serotonin modulates the properties of ascending commissural interneurons in the neonatal mouse spinal cord. (2006) J Neurophysiol. 95(3):1545-55. Epub 2005 Dec 7.

Díaz-Ríos M., and Miller M.W.  Rapid Dopaminergic Signaling by Interneurons that Contain Markers for Catecholamines and GABA in the Feeding Circuitry of Aplysia.  (2005) J. Neurophysiol. 93(4): 2142-56.

Walters E.T., Bodnarova M., Billy A.J., Dulin M.F., Diaz-Rios M., Miller M.W., and Moroz L.L. Somatotopic organization and functional properties of mechanosensory neurons expressing sensorin-A mRNA in Aplysia californica.  (2004) J. Comp. Neurol. 471(2); 219-240.

Wu J.S., Jing J., Díaz-Ríos M., Miller M.W., Kupfermann I. and Weiss K.R.  Identification of a GABA-containing Cerebral-Buccal Interneuron-11 in Aplysia californica. (2003) Neurosci. Lett.;341(1):5-8.

 

Funding

Ongoing:
1) NIH 1P20GM103642-01A1 Treistman (PD) / Diaz-Ríos (PI) 07/01/13 – 06/30/18

Center for Neuroplasticity at the University of Puerto Rico
Subproject title: The Role of Sensory Input to Mammalian Locomotion After the Loss of Supraspinal Inputs

Our long-term goal is to characterize the physiological mechanisms by which sensory input regulates and/or
controls the output properties of the spinal CPG network.
 
2) NSF 1337284 Miller (PI) 01/01/14 – 12/31/16
MRI: Acquisition of a Shared Laser Scanning Confocal Microscope at the Institute of Neurobiology
The goal of this grant is to acquire a state-of-the-art Laser Scanning Confocal Microscope (LSCM). This
instrument overcomes obstacles that previously limited the detection and precise localization of fluorescent
signals within nervous systems and other complex three-dimensional structures.
Role: Co-PI; no direct research support.

Completed:

1) DoD W911NF-07-R-002 Miller (PI) 09/01/07 – 08/31/09

Expansion of Imaging Facilities at the Institute of Neurobiology
The main goal of this proposal was to upgrade the existing confocal imaging facility located in the Institute of
Neurobiology (San Juan, PR), a facility that belongs to the University of Puerto (School of Medicine).
Role: Co-P.I; no direct research support.
 
2) 124554 - Craig Nielsen Foundation Díaz-Ríos (PI) 07/01/09 – 11/30/11
 
Sensory Information to Spinal Cord Interneurons after Injury
Our goal is to use the neonatal mouse spinal cord preparation to study how important sensory input to the spinal
cord circuitry through sensory feedback after injury is to the physiological “well being” of spinal interneuronal
populations.
Role: PI
 
3) NSF 0963179 Treistman (PI) 10/01/10 – 09/30/13
 
Renovation of the Institute of Neurobiology, University of Puerto Rico
The major goal of this project is to correct significant deficiencies including 1) an antiquated air conditioning
system and 2) an obsolete network cyberinfrastructure.
Role: Co-PI; no direct research support.
 
4) NSF 1026061 Díaz-Ríos (PI) 09/01/10 – 01/31/14
 
RIG: Identification of Pacemaker Neurons Controlling Locomotor Behavior
We will conduct a detailed and focused anatomical, physiological and biophysical characterization of the IIN
population
 
5) NSF 0932955 Miller (PI) 09/01/09 – 08/31/15
 
URM: Mentoring program in neural circuits and behavior at the Univ. of Puerto Rico.
The major goal of this project is to establish a mentoring program in neurobiology for 16 undergraduate
students at the University of Puerto Rico.
Role: Co-PI; no direct research support.

 

Recent Publications:
 
Ligand-specific endocytic dwell times control functional selectivity of the cannabinoid receptor 1.
Flores-Otero J, Ahn KH, Delgado-Peraza F, Mackie K, Kendall DA, Yudowski GA
Nat Commun. 2014 Aug 1.
 
Correction of mutations within the cystic fibrosis transmembrane conductance regulator by site-directed RNA editing.
Montiel-Gonzalez MF, Vallecillo-Viejo I, Yudowski GA, Rosenthal JJ.
Proc Natl Acad Sci U S A. 2013 Nov 5.
 
Acute inactivation of PSD-95 destabilizes AMPA receptors at hippocampal synapses.
Yudowski GA, Olsen O, Adesnik H, Marek KW, Bredt DS.
PLoS One. 2013.
 
Fast modulation of μ-opioid receptor (MOR) recycling is mediated by receptor agonists.
Roman-Vendrell C, Yu YJ, Yudowski GA.
J Biol Chem. 2012 Apr 27.
 
Investigating G protein-coupled receptor endocytosis and trafficking by TIR-FM.
Yudowski GA, von Zastrow M.
Methods Mol Biol. 2011
 
{Beta}-blocker drugs mediate calcium signaling in native central nervous system neurons by {beta}-arrestin-biased agonism.
Tzingounis AV, von Zastrow M, Yudowski GA.