Blazquez/Yakusheva Lab

Principal Investigators:
Pablo M. Blazquez, PhD, Associate Professor, Otolaryngology-Head & Neck Surgery
Tatyana A. Yakusheva, PhD, Assistant Professor, Otolaryngology-Head & Neck Surgery

Overview

Health problems associated with motor control and balance are the most common neurological disorders affecting the world population today. Our research is aimed to understanding motor control and balance in the normal and diseased brain, with the ultimate goal of paving the way towards finding cures and therapies for rehabilitation.

The goal of our research is to study the role of the vestibulo-cerebellum in motor control, balance and spatial navigation. The vestibulo-cerebellum is a region of the cerebellar cortex that comprises the floccular lobe and the posterior vermis. Currently, our lab is testing the hypothesis that the floccular lobe computes a forward model (predictive model) of the eye movement from vestibular and efferent copy information, and that the posterior vermis computes an estimate of our heading (translation) and orientation in space from semicircular canals and otolith information. Our experimental techniques include single unit recordings, pharmacology, behavioral neuroscience, mouse neurogenetics, histochemistry and computational modeling.

Golgi Cell

Research Projects

A leading hypothesis on cerebellar cortex function states that the cerebellar cortex generates predictions of the consequences of our movement (also called forward models) that are used for fine motor control and balance. We are currently testing this hypothesis in the two lobes that comprise the vestibulo-cerebellum: The floccular lobe and the posterior vermis (Nodulus and ventral Uvula). Our experimental techniques include single unit recordings, pharmacology, behavioral neuroscience, mouse neurogenetics, histochemistry and computational modeling.

Experimental design

The flocculus lobe

The most characteristic clinical manifestation of damage in the floccular lobe is the presence of downbeat nystagmus and the inability, or difficulty, in adapting the gain of the vestibulo-ocular reflex (e.g. during Meniere’s disease). We and others have shown that the floccular lobe combines vestibular and efferent copy information to generate appropriate commands that stabilize gaze during movements of the head and movements the object of interest. We have also shown that lesions in the floccular lode prevent the central nervous system from learning new associations between head movements and compensatory eye movements. Thus, the floccular node is necessary for normal pursuit behavior and to control the output of the vestibulo-ocular reflex (VOR). Our lab’s current research focuses on testing the hypothesis that the cerebellar flocculus computes an adaptable forward model of the eye movement from vestibular and efferent copy information. We are very interested in the role that cerebellar cortex interneurons play in these computations.

Vestibular neuron

The posterior vermis

The posterior vermis plays an essential role in balance control and spatial navigation. Our general hypothesis is that this structure uses information from the vestibular organs (semicircular canals and otoliths) to generate an estimate of our heading (translation) and orientation (tilt and roll) in space. We have previously published data supporting this view. We studied the information carried by input elements (mossy and climbing fibers) and by output elements (Purkinje cells) to the structure. Currently, we are using a mechanistic approach to study posterior vermis function. We are investigating the specific computations carried out by local circuit neurons in the posterior vermis as well as specific synapses.

Purkinje cells (Calbindin)

Current Funding

5R01DC016231: Pablo Blazquez (PI)
Title: Role of cerebellar cortex interneurons in cerebellar cortex function

5R01DC014276: Tatyana Yakusheva (PI)
Title: Vestibular signal processing carried out by the cerebellar nodulus and uvula

Lab Team

  • Pablo Blazquez, PhD
  • Tatyana Yakusheva, PhD
  • Fanetta Hampton
  • Val Militchin

Select Publications

  1. Blazquez PM, Kim G, Yakusheva TA. Searching for an Internal Representation of Stimulus Kinematics in the Response of Ventral Paraflocculus Purkinje Cells. Cerebellum. 2017
  2. Blazquez PM, Yakusheva TA. GABA-A Inhibition Shapes the Spatial and Temporal Response Properties of Purkinje Cells in the Macaque Cerebellum. Cell Rep. 2015 May 19;11(7):1043-53.
  3. Meng H, Laurens J, Blázquez PM, Angelaki DE. In vivo properties of cerebellar interneurons in the macaque caudal vestibular vermis. J Physiol. 2014. Nov 10. [Epub ahead of print]
  4. Meng H, Blázquez PM, Dickman JD, Angelaki DE. Diversity of vestibular nuclei neurons targeted by cerebellar nodulus inhibition. J Physiol. 2014.
  5. Yakusheva TA, Blazquez PM, Chen A, Angelaki DE. Spatiotemporal properties of optic flow and vestibular tuning in the cerebellar nodulus and uvula. J Neurosci. 2013 33(38):15145-60. 
  6. Laurens J, Heiney SM, Kim G, Blazquez PM. Cerebellar cortex granular layer interneurons in the macaque monkey are functionally driven by mossy fiber pathways through net excitation or inhibition. PLoS One, 2013.
  7. Yakusheva TA, Blazquez PM, Chen A, Angelaki DE. Spatiotemporal properties of optic flow and vestibular tuning in the cerebellar nodulus and uvula. J Neurosci. 2013 33(38):15145-60.
  8. Van Dijck G, Van Hulle MM, Heiney SA, Blazquez PM, Meng H, Angelaki DE, Arenz A, Margrie TW, Mostofi A, Edgley S, Bengtsson F, Ekerot CF, Jörntell H, Dalley JW, Holtzman T. Probabilistic identification of cerebellar cortical neurones across species. PLoS One. 2013
  9. Partsalis, A.M., Blazquez, P.M., Triarhou, L.C. The renaissance of the neuron doctrine: Cajal rebuts the rector of granada. Translational Neuroscience 2013. 4 (1) pp. 104-114
  10. Heine SA and Blazquez PM. Behavioral responses of trained squirrel and rhesus monkeys during oculomotor tasks. Exp Brain Res. 2011 Jul;212(3):409-16
  11. Heine SA and Blazquez PM. Thinking Inside the box: The roles of inhibitory interneurons in cerebellar processing. Jap J. of Neuronal Netw. 2011.
  12. Heiney SA, Highstein SM, Blazquez PM. Golgi cells operate as state-specific temporal filters at the input stage of the cerebellar cortex. J. Neurosci. 2010 Dec 15;30(50): 17004-14
  13. Yakusheva T,Blazquez PM, Angelaki DE. Relationship between complex and simple spike activity in macaque caudal vermis during three-dimensional vestibular stimulation. J Neurosci., 2010, 30(24):8111-26.
  14. Angelaki DE, Yakusheva TA, Green AM, Dickman JD, Blazquez PM Computation of Egomotion in the Macaque Cerebellar Vermis. Cerebellum. 2009 Dec 11.
  15. Inagaki K, Hirata Y, Blazquez PM, Highstein SM. Computer Simulation of Vestibuloocular Reflex Motor Learning Using a Realistic Cerebellar Cortical Neuronal Network Model. Neural Information Processing. Lecture Notes in Computer Science, 2008, Volume 4984: 902-912.
  16. Inagaki K, Heiney SA, Blazquez PM. Method for the construction and use of carbon fiber multibarrel electrodes for deep brain recordings in the alert animal. J Neurosci Methods. 2009 Apr 15;178(2):255-62.
  17. Yakusheva TA, Blazquez PM, Angelaki DE. “Frequency-selective coding of translation and tilt in macaque cerebellar nodulus and uvula”. J Neurosci. 2008 Oct1; 28 (40):9997-10009. 
  18.  Blazquez PM and Highstein SM. “Visual-vestibular interaction in vertical vestibular only neurons”. Neuroreport, 2007, 18 (3): 1403-1406.
  19. Yakusleva T, Shaikh AG, Green AM, Blazquez PM, Dickman JD, and Angelaki DE. “Purkinje cells in posterior vermis detect motion in an inertial reference frame”. Neuron, 2007, 54(6): 973-85.
  20. Blazquez PM, Davis-Lopez de Carrizosa M, Heiney SA, and Highstein SM. “Neuronal substrates of motor learning in the velocity storage generated during optokinetic stimulation in the squirrel monkey” J Neurophysiol. 2007, 97(2): 1114-26.
  21. Hirata Y, Blazquez PM and Highstein SM (2006) Identification of loci involved in the memory of chronic motor learning of the vertical vestibuloocular reflex in squirrel monkeys”. Cerebellum 5 (4), 296-297.
  22. Blazquez PM, Hirata Y, Highstein SM. “Chronic changes in inputs to dorsal Y neurons accompany VOR motor learning”. J Neurophysiol. 2006, 95(3):1812-25.
  23. Hirata Y, Yoshikawa A, Blazquez PM, Highstein SM. “Evaluation of the inverse dynamic model in the cerebellum during visual-vestibular interactions at different VOR gains in the squirrel monkeys”. Neurocomputing 65-66: 709-717 (2005).
  24. Blazquez PM, Hirata Y, Highstein SM. “The vestibulo-ocular reflex as a model system for motor learning: what is the role of the cerebellum?” Cerebellum. 2004, 3(3):188-92.
  25. Y. Kuki, Y. Hirata, Blazquez PM, SA Heiney, SM Highstein. “Memory retention of the Vestibulo-ocular Reflex Motor Learning in Squirrel Monkeys”. Neuroreport. 2004 Apr 12;15(6):1007-11.
  26. Blazquez PM, Hirata Y, Heiney S.A., Green A.M., Highstein S.M. ”Cerebellar signatures of vestibulo-ocular reflex motor learning” J Neurosci 2003;23(30):9742-51.
  27. Blazquez PM, Fujii N, Kojima J and A.M. Graybiel. “A network representation of response probability in the striatum”. Neuron. 2002 Mar 14; 33(6):973-82.
  28. Blazquez PM, Partsalis A, Gerrits NM, Highstein SM. “Input of anterior and posterior semicircular canal interneurons encoding head-velocity to the dorsal Y group of the vestibular nuclei”. J Neurophysiol. 2000 May;83(5):2891-904.
  29. Gruart A, Blazquez PM, Delgado-Garcia JM. “Kinematics of spontaneous, reflex, and conditioned eyelid movements in the alert cat”. J Neurophysiol. 1995 Jul;74(1):226-48.
  30. Gruart A, Blazquez PM, Delgado-Garcia JM. “Kinematic analyses of classically-conditioned eyelid movements in the cat suggest a brain stem site for motor learning”. Neurosci Lett. 1994 Jul 4;175(1-2):81-
  31. Gruart A, Blazquez PM, Pastor AM, Delgado-Garcia JM. “Very short-term potentiation of climbing fiber effects on deep cerebellar nuclei neurons by conditioning stimulation of mossy fiber afferents”. Exp Brain Res. 1994;101(1):173-7.

Software

This software will be released under the MIT open source License (https://opensource.org/licenses/MIT). We are currently cleaning up the code to make it user friendly. Software would be available upon request.

DATA ACQUISITION:

TwelveMonkeys: Acquisition program to train non-human primates in oculomotor tasks. Written for Visual Pascal Version (Delphi 6.0), Visual Basic, and Spike 2 (Cambridge Electronic Design).

TiltTransl4Mouse: Controls linear and angular motion of our sled system. Currently, it allows only sinusoidal stimulation. Written for Spike2.

Simple Scope: It uses the phone jack of the computer (laptop) to record 1 analogue channel (through the microphone) and to output two analogue channels (through the stereo speaker). Written for matlab.

DATA ANALYSIS:

Full analysis programs:
Monk4LabV02: Main analysis programs related to : sort trials based on direction of movement, correct vs. incorrect, type of stimulation, etc. Written for matlab.

MouseAnalysisV06_1: General sinusoidal data analysis. Average analogue (up to 5 channels) and neuronal (up to two channels) data over trials. Provides the gain, phase, DC and p value of the sinusoidal fitting function. Written for matlab.

MainAveV12: A program created to analyze mainly sinusoidal OKR and VOR data. Written for matlab.

Functions
DesaccadeData: Provide the indexes of the data set that do not contain saccades Written for matlab.

Ruigrok: Classify cerebellar cortex interneurons according to Ruigrok et al. 2011 method. Written for matlab.

We express our gratitude to the OPEN SOURCE COMMUNITY for providing valuable comments and functions.

Contact Us

Mailing address

660 S. Euclid Ave.
Campus Box 8115
St.Louis, MO 63110

Physical address

4566 Scott Ave.
St. Louis, MO 63110

Email

pablo@wustl.edu

yakushevat@wustl.edu