Dr Robert Pawlak

Research Interests and Techniques

Neural Bases of Behaviour

Introduction

We are interested in cellular mechanisms involved in experience-induced neuronal plasticity underlying learning, fear and anxiety.

See also www.pawlaklab.com for more information

Research

Psychological stress induces neuronal responses that can be either adaptive and directed toward maintaining homeostasis, or maladaptive leading to severe behavioural abnormalities. However, molecular mechanisms underlying the development of stress-induced disorders, such as cognitive impairment, anxiety and depression are poorly understood.

Fig.1 Spine density is reduced in the medial amygdala (MeA) in wild-type mice exposed to restraint stress (Stress). Photomicrographs of representative segments of primary branches from unstressed (left) and stressed (right) mice. (Scale bar = 10 m m). Mean ( +SEM) values for spine-density of primary branches of spiny MeA neurons from No Stress and Stress groups, demonstrating decrease in the number of spines. MeA - medial amygdala; CA – central amygdala. Study done in collaboration with Drs B McEwen, S Chattarji and S Strickland.

Two brain regions critically involved in stress-induced behavioural abnormalities is the amygdala and the hippocampus. We have recently demonstrated that, after stress, serine proteases mediate neuronal plasticity in these areas, and are critical for the development of anxiety.

We are interested in the molecular machinery that proteases use to facilitate neuronal plasticity, learning and anxiety. We study that using genetic, cell biological, pharmacological and electrophysiological approaches. We correlate these studies with behavioural experiments in mice deficient for specific proteases or their molecular partners.

Figure 2. The expression of a serine protease, tissue plasminogen activator (tPA) in the amygdala and its regulation by restraint stress . (Upper panels) The anatomical organization of the amygdala visible on cresyl violet-stained section (left) helps identify tPA immunoreactivity (red in the middle panel) and activity (dark lytic zones on in situ zymography, right panel) in central (CA) and medial (MeA) amygdala. (Lower panels) In situ zymography of extracellular tPA activity (dark lytic zones) shows that in basal conditions (No Stress, left panel) tPA is active in the hippocampal mossy fiber pathway and in the central and medial amygdala (CA and MeA). Extracellular tPA activity increased after 30 min of restraint stress (middle panel) and was subsequently inhibited 6 hours later (right panel).

Research Group and Funding

Current Members

Ben Attwood
Julie-Myrtille Bourgognon
Satyam Patel

Current Funding

MRC Project Grant
ABMRF Research Grant
Marie Curie Excellence Grant (European Commission) 2007-2011 €1.7 million

Collaborators

Dr Sumantra 'Shona' Chattarji (National Centre for Biologica Sciences, Bangalore, India)
Dr Bruce McEwen (The Rockefeller University, New York, USA)
Professor Ian Forsythe (University of Leicester, UK)
Dr Sidney Strickland (The Rockefeller University, New York, USA)

Recent Publications

Bennur S, BS Shankaranarayana Rao, Pawlak R, Strickland S, McEwen BS, Chattarji S. Stress-induced spine loss in the medial amygdala is mediated by tissue-plasminogen activator. Neuroscience 2007, 144(1):8-16.

Pawlak R, BS Shankaranarayana Rao, Melchor JP, Chattarji S, McEwen B, Strickland S. Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Proc Natl Acad Sci U S A 2005, 112(50): 18201-18206.

Pawlak R, Melchor JP, Matys T, Skrzypiec AE and Strickland S. Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors. Proc Natl Acad Sci U S A 2005, 102(2), 443-448.
Media coverage: In English, In Polish, In Russian
Commentaries: AESnet, The Lancet

Matys T, Pawlak R, Matys E, Pavlides C, McEwen BS, Strickland S: Tissue plasminogen activator promotes the effects of corticotropin-releasing factor on the amygdala and anxiety-like behavior. Proc Natl Acad Sci U S A 2004, 101(46), 16345-16350.

Pawlak R, Magarinos AM, Melchor JP, McEwen B, Strickland S: Tissue-plasminogen activator in the amygdala is critical for anxiety-like behavior. Nature Neuroscience 2003, 6( 2): 168-174
Media coverage: Australia
Commentary: ScienceDirect

Melchor JP, Pawlak R, Strickland S: The tPA/plasminogen proteolytic cascade accelerates Aß degradation and inhibits Aß-induced neurodegeneration. J Neurosci 2003, 23( 26): 8867- 8871