Jason MacLean, PhD Assistant Professor Department of Neurobiology The University of Chicago 947 E. 58th St., MC0926 Chicago, IL 60637 Email: jmaclean@bsd.uchicago.edu Phone: (773) 834-7650 Office: SBRI J111 (MC 0926)

Research Summary

Optical probing and imaging of neuronal microcircuits.

Research Description

My research interests focus on the understanding of neuronal networks at many levels of investigation. I have explored single channel and molecular questions as well as network-wide computational questions in many different networks including the neocortex, the spinal cord and the lobster stomatogastric ganglion. In my lab I am using advanced imaging techniques including 2-photon laser scanning microscopy, in combination with patch clamp physiology to explore local circuits in the mammalian central nervous system. I delineate circuits according to the component neurons, the connections between them and the dynamics that they exhibit spontaneously and when a meaningful input is supplied. Finally I examine which computation theoretical framework best explains the overall organization of the microcircuit based on the data generated.

Cortex: Using calcium imaging in somatosensory thalamocortical slices, I have reconstructed with single cell resolution the spatiotemporal dynamics of activity of populations of layer 4 neurons in cortex. I observed that synchronous activations of ensembles of neurons, which correspond intracellularly to periods of prolonged depolarization, or UP states, arise spontaneously in the cortex. Further, thalamic stimulation which elicits 'burst type' activity in thalamic relay neurons is capable of triggering ensemble activations and UP states which are highly similar to the ensembles and UP states arising spontaneously. Moreover, in both thalamically triggered and spontaneous events, neurons are activated in significantly overlapping and complex spatiotemporal patterns. Finally I demonstrated that these spatiotemporal dynamics are generated by cortex itself and not the thalamus.

The striking similarity and the cortical origin of the spontaneous dynamics suggest that intracortical connectivity plays a dominant role in the cortical response to thalamic input (MacLean et al. 2005, Neuron). Indeed, there is increasing evidence that the spontaneous cortical activity which I have been characterizing in vitro also occurs in vivo in the awake animal.

Spinal Cord: The cellular components and organization of the spinal cord locomotor central pattern generator (CPG ) or microcircuit are to date undefined. However, the existing data suggest that CPG circuits share profound similarities with neocortical circuits. The spinal cord locomotor CPG will be explored using a comparable approach which I have applied to the cortex including imaging of network dynamics combined with physiology, morphology, computational theory. In this way my laboratory will identify important interneurons in the locomotor CPG of the mouse.

Using both systems I intend to examine each individual circuit and determine what general principles define and govern microcircuit organization throughout the central nervous system.

Some Selected Papers

MacLean, J. N., Fenstermaker, V., Watson, B. O., and Yuste, R. (2006) A Mouse Visual Thalamocortical Slice. Nature Methods. 3: 129-134.

MacLean, J. N., Watson, B. O., Aaron, G. B., and Yuste, R. (2005) Internal dynamics determine the cortical response to thalamic stimulation. Neuron. 48: 811-823.

Yuste R., MacLean, J.N., Smith, J. and Lanser, A.(2005). Perspective/Opinion: Can CPGs help us understand cortical function? Nature Rev Neurosci., 6: 477-83

MacLean, J.N., Zhang, Y., Johnson, B.J. and Harris-Warrick, R.M. (2003) Activity-Independent Homeostasis in Rhythmically Active Neurons. Neuron 37: 109-120.

MacLean, J.N. and Schmidt, B.J. (2001). Voltage-sensitivity of motoneuron NMDA receptor channels is modulated by serotonin in the neonatal rat spinal cord. J Neurophysiol 86: 1131-1138

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