An emerging trend in neuroscience and neurophysiology is the movement towards understanding the fundamental behavior of neurons at the ensemble or population level by studying individual neurons at multiple sites. Electrophysiology of populations of neurons is greatly aided by the development of multi-channel or array electrodes by integrated circuit (IC) technology. However, there is considerable heterogeneity in the distribution and function of neurochemical elements as well. Therefore, a technology that enables simultaneous monitoring of neurochemical activity at different locations in the brain promises to make fundamental discoveries in regional heterogeneity and specialization of neurochemistry of brain tissue. Further, if the electrical activity of a population of neurons as well as the complementary neurotransmitter activity could be localized and measured concurrently, it could unify two important domains: electrophysiology and neurochemistry/pharmacology. The central goal of this proposal is to develop a novel microsensor technology for providing real time, continuous measurement of both neurotransmitter and neuronal electrical activity. The underlying novel idea is to construct a carbon-based microsensor array that will capture neurotransmitter and electrical activity from multiple neurons. Specifically, the microsensor array will be developed for measuring the diffusible messenger nitric oxide (NO) and the neuronal electrical response accompanying NO activity. The sensor will be tested in an in vitro model (hippocampai brain slice) in which the distribution of NO and its role in modulating the excitability of neurons in different regions of the slice will be studied. Fundamental technical barriers that must be overcome are: 1) Development of a carbon-based microsensor technology by utilizing novel screen printing and photolithographic processing techniques. 2) Combining electrical and electrochemical sensing on a single substrate and interfacing this sensor array to the brain tissue. This technology offers a revolutionary advance in neurophysiology research: it will potentially break down the barrier that exists in neuroscience, between the fields of pharmacological neuroscience and electrophysiologic neuroscience. The coupling of these two basic neural responses, electrical and chemical, would shift the prevailing paradigm of neuroscience research pertaining to neurological diseases or mental health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH062444-01A1
Application #
6382745
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (10))
Program Officer
Huerta, Michael F
Project Start
2001-09-17
Project End
2003-07-31
Budget Start
2001-09-17
Budget End
2002-07-31
Support Year
1
Fiscal Year
2001
Total Cost
$154,375
Indirect Cost
Name
Johns Hopkins University
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Mollazadeh, M; Murari, K; Cauwenberghs, G et al. (2009) Micropower CMOS Integrated Low-Noise Amplification, Filtering, and Digitization of Multimodal Neuropotentials. IEEE Trans Biomed Circuits Syst 3:1-10
Mollazadeh, Mohsen; Murari, Kartikeya; Cauwenberghs, Gert et al. (2008) From spikes to EEG: integrated multichannel and selective acquisition of neuropotentials. Conf Proc IEEE Eng Med Biol Soc 2008:2741-4
Murari, Kartikeya; Stanacevic, Milutin; Cauwenberghs, Gert et al. (2005) Integrated potentiostat for neurotransmitter sensing. A high sensitivity, wide range VLSI design and chip. IEEE Eng Med Biol Mag 24:23-9