Phone: (706) 721-8901
Fax: (706) 721-7299

Email: JFilosa@mcg.edu
Office: CA-2092

My major research interest is to gain understanding of the signaling mechanisms governing bi-directional communication among the various cell types within the brain.  In particularly, I am interested in the communication between neurons and their surrounding glial and vascular cells.  Recent findings have demonstrated an important role for astrocytes as intercellular bridges between the state of neuronal activity and vascular dynamics (or neurovascular coupling). These findings have lead to a number of different hypotheses addressing the potential role astrocytes have in neurovascular coupling.  However, major gaps in our knowledge are still present in regards to: the nature of the signals released (both by neurons and astrocytes during the hyperemic response), the mechanisms by which astrocytes decode various degrees of neuronal activities, and the targets (ion channels and receptors) involved.  Until recently, the small size and location of parenchymal arterioles precluded us from studying the intrinsic mechanisms governing the dynamics of these microvessels.  Today’s technology allows us to explore the cellular signals controlling parenchymal microvessels in the brain.  I believe this is an important area of research that merges our basic understanding of neuroscience with that of cardiovascular physiology.  Furthermore, I believe understanding the communication between these two major systems will increase awareness on pathologies known to show vascular and neuronal deteriorations, including hypertension, diabetes, Alzheimer’s disease and stroke.

Major focus interest in our laboratory include:

• To characterize the intrinsic properties of parenchymal arterioles in the brain.
• To characterize neuron-glial-vascular communication in different specialized brain regions
• To determine the role changes in the mechanisms underlying the crosstalk between neuron glial-vascular communications plays in the patho-physiology of cerebrovascular disorders such as hypertension and stroke.

• To characterize the intrinsic properties of parenchymal arterioles in the brain. The neurovascular control of the cerebral microcirculation varies depending on the location and caliber of the vessels.  One of our major goals is to characterize the intrinsic properties of parenchymal microvessels from different brain areas, the types of ion channels that control their resting membrane potential and their intrinsic intracellular Ca2+ signaling mechanisms.  These studies are conducted using a variety of techniques including electrophysiological recordings from isolated vascular smooth muscle cells from different arterioles (size and location) as well as intracellular Ca2+ signaling and regulation using high speed confocal Ca2+ imaging in the brain slice preparation.

 

• To characterize neuron-glial-vascular communication in different specialized brain regions. Most of the studies conducted on functional hyperemia have focused primarily on the cerebral cortex.  However, mechanisms underlying neurovascular coupling are most likely dependent not only on the types of signals (neurotransmitters & neuromodulators) available in a specific brain area, but also on the neuronal circuits projecting to that area as well.  We are currently studying neuro-glia-vascular communication in three main brain areas inlcuding: the somatosensory cortex, the supraoptic nucleus and the hypothalamus.  We use a combination of state-of-the-art techniques that allows us to define the functional and anatomical changes observed in neurons, glia and vascular cells in response to a given stimulus. To this end, we are currently looking at the electrophysiological activity of different neuronal populations, their impact on astrocytic activity and the overall vascular dynamic changes resulting from these events.  Electrophysiological studies are also combined with Ca2+ imaging to further understand the mode of communication from one cell type to the other, and to determine if the degree of synaptic activity is decoded by astrocytes which signal parenchymal arterioles to either dilate or constrict.

 

• To determine the role changes in the mechanisms underlying the crosstalk between neuron glial-vascular communications plays in the patho-physiology of cerebrovascular disorders such as hypertension and stroke.  Abnormalities in vascular and/or astrocytic function highly compromise neuronal function.  This project focuses on disturbances in the mechanisms bridging neuro-glia-vascular communication and their contribution to cerebrovascular abnormalities observed during hypertension.  These studies will shed light on the mechanisms underlying chronic hypertension and how these changes increase the vulnerability to stroke.  These studies involved electrophysiology, Ca2+ imaging and immunohistochemistry techniques in a hypertensive model (Goldblatt model of renovascular hypertension).  These techniques allow us to address both functional and anatomical alterations in neuro-glia-vascular communication during the different stages of hypertension.  We are also interested in characterizing the anatomical alterations of the neurovascular unit throughout the onset and maintenance of hypertension to determine if these pathologies results in the disruption of the intercellular communication between active neurons and its surrounding microcirculation.

Haruki Higashimori , Postdoctoral Fellow

Go to PubMed

Blanco VM, Stern JE, Filosa JA.  Tone-dependent vascular responses to astrocyte-derived signals.  Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2855-63.

Sonner PM, Filosa JA, Stern JE.  Diminished A-type potassium current and altered firing properties in presympathetic PVN neurones in renovascular hypertensive rats.

J Physiol. 2008 Mar 15;586(6):1605-22.

Filosa JA, Nelson MT, Gonzalez Bosc LV.  Activity-dependent NFATc3 nuclear accumulation in pericytes from cortical parenchymal microvessels.  Am J Physiol Cell Physiol. 2007 Dec;293(6):C1797-805

Filosa JA, Blanco VM.  Neurovascular coupling in the mammalian brain.  Exp Physiol. 2007 Jul;92(4):641-6

Filosa JA, Bonev AD, Straub SV, Meredith AL, Wilkerson MK, Aldrich RW, Nelson MT.

Local potassium signaling couples neuronal activity to vasodilation in the brain.

Nat Neurosci. 2006 Nov;9(11):1397-1403.

Clark JF, Doepke A, Filosa JA, Wardle RL, Lu A, Meeker TJ, Pyne-Geithman GJ.  N-acetylaspartate as a reservoir for glutamate. Med Hypotheses. 2006;67(3):506-12.

Putnam RW, Filosa JA, Ritucci NA.  Cellular mechanisms involved in CO(2) and acid signaling in chemosensitive neurons.  Am J Physiol Cell Physiol. 2004 Dec;287(6):C1493-526. Review.

Filosa JA, Bonev AD, Nelson MT.  Calcium dynamics in cortical astrocytes and arterioles during neurovascular coupling. Circ Res. 2004 Nov 12;95(10):e73-81. Epub 2004 Oct 21.

Filosa JA, Putnam RW.  Multiple targets of chemosensitive signaling in locus coeruleus neurons: role of K+ and Ca2+ channels.  Am J Physiol Cell Physiol. 2003 Jan;284(1):C145-55.

Filosa JA, Dean JB, Putnam RW.  Role of intracellular and extracellular pH in the chemosensitive response of rat locus coeruleus neurones.  J Physiol. 2002 Jun 1;541(Pt 2):493-509.