Research 

Research Areas

  • Parkinson's Disease and Addiction
  • Modeling/Software
  • Synaptic Plasticity in the Hippocampus
  • Theoretical and Experimental Investigations of the Basal Ganglia

    How does the lack of dopamine produce the symptoms of Parkinson's Disease???
    How does excessive dopamine in response to drugs of abuse produce addiction???

  • We utilize electrophysiology, optogenetics and behavior to investigate how dopamine and other neuromodulators controls the synaptic plasticity that underlies learning.

    Read more about our new theta burst stimulation paradigm for inducing LTP in normal magnesium.


  • We develop single neuron models with detailed calcium dynamics in order to investigate how temporal stimulation patterns control synaptic plasticity.

    How do neurons "know" to strengthen synapses that are consistently active? Are nearby synapses affected (spatial specificity)? Read more here.

  • We create biophysically realistic, computational models of striatal neuronal networks to investigate how dopamine depletion produces abnormal brain rhythms and oscillations.

    Large scale simulations of striatal network models reveals that the abnormal connectivity between striatal neurons causes beta oscillations. Dopamine depletion weakens the lateral inhibitory connections, and strengthens the feedforward inhibition from fast spiking interneurons. Synchronizing input to the gap junction connected FSIs produces beta band oscillations. A prediction of the model is that blocking gap junctions will normalize striatal activity and restore normal movement in Parkinson's Disease. Read more about this research here.


  • Striatal Network Model
  • We develop novel computational algorithms for modeling the signaling pathways underlying synaptic plasticity, in order to understand how dopamine influences memory storage.



  • Mechanisms underlying Hippocampal LTP

  • We investigated mechanisms underlying temporal sensitivity of PKA. Specifically, why is PKA required for long lasting LTP is induced using 4 trains separated by 300 sec, but not when 4 trains are separated by 3 sec? Our simulations showed that PKA activity increases with increasing intertrain interval, whereas CaMKII activity decreases with increasing intertrain interval. Read more about this research here.
  • Then we developed a spatial Monte Carlo model to investigate the role of PKA anchoring. Our simulations demonstrate that PKA needs to be anchored near adenylyl cyclase, because phosphodiesterases limit the diffusional range of cAMP. This research was published in 2011.
    We are now creating a unifying model of signaling pathways underlying hippocampal LTP that can predict the plasticity outcome of all stimulation paradigms.


  • Software Development for Modeling Signaling Pathways

  • We have developed new software for computationally efficient modeling of stochastic reaction-diffusion systems. The mesoscopic algorithm is an extension of Gillespie's Tau-Leap algorithm in to the diffusion domain. The software has been used to model signaling pathways underlying hippocampal and striatal synaptic plasticity, both LTP and LTD
  • This software, written in java, is freely available. A README file, Tutorial and example files explain how to specify models in xml.
  • We are continuing to develop this software, to make it more efficient and more accurate.
  • A usefullisting of other software for simulating stochastic reaction-diffusion systems


  • Other useful neural modeling software:

    GENESIS Home Page

    Chemesis libraries for modeling biochemical reactions and calcium dynamics.

    NEURON Home Page

    XPP (Bard Home Page)

    home Research Personnel Publications Software Positions Avrama
    Blackwell

    Revised: 07/2011 - Avrama Blackwell