Francisco J. Alvarez, PhD
The principal interest of our lab is the development and plasticity of synaptic circuits in functional networks. More specifically our lab focuses on spinal motor circuit assembly during development resulting in the formation of spinal circuits capable of adult-like locomotion. In other words we study how newborns "learn to walk". Within these circuits our main interest is on the specification, synaptogenesis and maturation of the neurochemical and electrophysiological properties of inhibitory interneurons (like Renshaw cells and Ia inhibitory interneurons) that modulate and pattern the activity of motoneurons.
This basic understanding then constitutes the knowledge foundation to analyze how these circuits are modified after injury or during neurodegenerative disease. In one project we study how spinal premotor circuits are modified by peripheral nerve injury and what prevents them from recovery. This project seeks an explanation to motor deficits, for example lack of monosynaptic stretch reflexes, that linger in patients with peripheral nerve injuries or neuropathies even after the peripheral nerve has undergone normal regeneration and muscle reinnervation.
In other projects we study the progressive transformation of some of these circuits in motor neurodegenerative diseases like amyotrophic lateral sclerosis and spinal muscular atrophy. The goal is to provide mechanistic explanations on the progression of symptoms and uncover synaptic level processes that might enhance the motor dysfunction and/or the motoneuron demise.
The lab uses multidisciplinary approaches that include modern neuroanatomical methods (3D and 4D analyses of confocal, two-photon and electron microscopy images) and in vitro electrophysiology (patch-clamp recordings in spinal cord slices) in a number of rodent models, including several lines of transgenics for genetic labeling or modification of specific subtypes of interneurons or modeling human diseases. In some of these projects we greatly benefit from long-term collaborations with investigators in other institutions (Wright State University, Columbia University, Salk Institute) that provide our lab with key expertise in aspects of mouse molecular genetics and in vivo rat spinal cord electrophysiology.