PUBLICATIONS:

BOOK CHAPTERS

RESEARCH PROJECT

"Cambios estacionales en el cerebro: mecanismos neuronales de las señales de cortejo en el pez eléctrico autóctono Brachyhypopomus pinnicaudatus" Financiado por Dinacyt, Fondo Clemente Estable. Responsable: O. Macadar.

1. Research Interests of Laboratory of cellular microbiology

During the recent years the main goal of my research has been to investigate the cellular and synaptic mechanisms implicated in early stages of somatosensory information processing. The initial analysis of somatosensory information takes place in the dorsal horn of the spinal cord where the information carried by primary afferents is integrated by second order neurons. To study the complex interactions that occur at this level I use electrophysiological techniques such as extracellular, intracellular and whole-cell patch-clamp recordings in a variety of in vitro preparations of the spinal cord of freshwater turtles. My current research interests range from the cellular and molecular to the systems level of integration and can be grouped in four main lines of research.

• Cellular and molecular mechanisms of somatosensory information processing.

The intrinsic electrophysiological properties of neurons represent a fundamental building block for the overall performance of neural networks. A major goal of my research is to study the contribution of the intrinsic properties of dorsal horn neurons (DHN) to the integration of sensory information. In transverse slices of the spinal cord, we found that integration of primary afferent mediated inputs is strongly biased by the particular intrinsic responsiveness of DHN.1,2,3 For example, some neurons integrate information on a time scale of seconds due to a plateau potential mediated by L-type Ca2+ channels. An important finding is that the ”windup” phenomenon -a short-lasting, activity-dependent type of plasticity related to pain mechanisms- is generated mainly by the progressive activation of the plateau potential.1,2. The plateau potential and thus the ”windup” phenomenon are regulated via metabotropic receptors by transmitters such as glutamate and substance P, 4 which are known to be co-released by nociceptive fibers. As in other neurons in the central nervous system, direct modulation of Ca2+ channels by activity or neurotransmitters is bound to be a major way for fine tuning the intrinsic responsiveness of DHN. An important issue to be addressed in my future research is the basic molecular mechanism for “windup” generation: is “windup” due to activity-dependent facilitation of L-type Ca2+ channels as in other cell types? A second related problem is the interaction between activity-dependent modulation and neurotransmitter induced modulation: are they independent forms of regulation of intrinsic responsiveness or do they share common mechanisms? I plan to answer these questions using patch-clamp recordings of isolated dorsal horn cells combined with the use of selective drugs with different application methods.

• Regulation of synaptic efficacy of primary afferents.

An important way for regulation of information transfer is by modulation of synaptic efficacy at the presynaptic level. A conspicuous example of this in the somatosensory system is the presynaptic inhibition of sensory fibers whose electrophysiological correlate is the primary afferent depolarization (PAD). I explore the mechanisms of PAD generation by recording extracellularly the PAD in an enlarged in vitro preparation of the spinal cord. We recently found that a significant component of the PAD is generated by a non-spiking microcircuit with both GABAergic and glutamatergic components.5 This resembles the complex integration by microcircuits in the olfactory bulb and the retina and suggests a general strategy for early sensory information processing. I am now interested in revealing the nature of the microcircuit which implicates the combination of electrophysiological and anatomical studies. The key questions are: what is source and the mechanisms of release of GABA by the microcircuit? Is the glutamatergic component due to volume conduction? Another important point to address is the functional relevance of the PAD generated by the microcircuit. For example: does the non-spiking mediated PAD produce a decrease of synaptic efficacy or under some circumstances can produce facilitation?

• Role of intrinsic properties in the analysis of somatosensory information.

Although our previous studies have demonstrated that the active properties of dorsal horn neurons can “shape” primary afferent mediated inputs that under normal conditions carry sensory information, the synchronous activation of afferent fibers with electric shocks is just a caricature of a real, meaningful sensory input. A more rigorous analysis of the role of intrinsic properties in sensory information processing has to be pursued in a more intact preparation that combines the advantages of in vitro preparations with the capability of eliciting a more relevant input from the sensory point of view. Taking advantage of the outstanding resistance to hypoxia of freshwater turtles, I have developed a preparation which keeps the hindlimbs and part of the carapace intact while the lumbar enlargement of the spinal cord is exposed and superfused with Ringer as in in vitro preparations. Using the “whole-cell” recording technique I have been able to record DHN that show basically the same properties of those recorded in conventional slices and can be activated by natural stimulation (mechanical, chemical or heat) applied to the legs or the carapace. I feel sure that this preparation is an ideal model for the study of the role of active membrane properties in phenomena such as “ameboid” receptive fields and plastic changes like those observed in hyperalgesia and allodinia after stimulation of nociceptive fibers.

• Neurogenesis in the post-natal spinal cord.

In collaboration with the group of Dr. Trujillo-Cenóz, I have recently started to study the functional aspects of neurogenesis in the spinal cord of juvenile turtles. In this unique model, we have the opportunity to explore the maturation of the excitability of newborn neurons and to characterize the functional incorporation of these cells to already operating spinal circuits.

Selected References.
1. Russo, R.E. and J. Hounsgaard (1994) Neuroscience. 61: 191-197.
2. Russo, R.E. and J. Hounsgaard (1996) J. Physiol.(London) 493: 39-54.
3. Russo, R.E. and J. Hounsgaard (1996) J. Physiol.(London) 493: 55-66.
4. Russo, R. E. et al. (1997) J. Physiol.(London) 499: 459-474
5. Russo, R.E. et al. (2000) J. Physiol. 528: 115-122.