This project aims to elucidate the cellular mechanisms that allow a neural network to produce stable output while retaining the flexibility to respond to perturbations, such as those that occur during growth, learning, sensory input and injury. Ionic currents produce the electrical changes that characterize neuronal activity, and individual neurons and neural networks are responsible for the generation of behavior. In so doing, the nervous system and its parts are often capable of homeostatically restoring their properties after a perturbation or damage. Several mechanisms allow this process of stabilization or restoration of activity to be expressed, the best studied of which is perhaps synaptic plasticity. However, a different mechanism is emerging as a powerful candidate to underlie the expression of these two seemingly paradoxical aspects of neuronal activity of flexibility and stability. This mechanism is activity-dependent regulation of voltage-sensitive ionic currents. In this proposal a series of experiments is described to study the properties of this poorly understood mechanism of neuronal activity regulation. This mechanism is potentially of great importance as it may underlie a new form of learning and memory via its stabilizing effect on neural network activity. The regulation of activity in a small and well-characterized neural network, as well as the role of long-term activity-dependent regulation of ionic currents in this process will be investigated. Previous work has shown some evidence of long-term interactions and mutual regulation between different ionic currents. I will investigate in depth these mutual regulatory interactions and their possible role in the process of stabilization of neuronal activity. The experimental methodology will include several modes of electrophysiological recording of neurons in the intact network in vitro, in the intact network in the living a freely moving animal, in dissociated cells in culture, and in long-term culture of the whole network. Pharmacological manipulations, as well as RNA injections of recently cloned ionic channels, will be used to modify the expression of endogenous ionic currents.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Glanzman, Dennis L
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Rutgers University
Biostatistics & Other Math Sci
Schools of Arts and Sciences
United States
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Gray, Michael; Golowasch, Jorge (2016) Voltage Dependence of a Neuromodulator-Activated Ionic Current. eNeuro 3:
Golowasch, Jorge (2014) Ionic Current Variability and Functional Stability in the Nervous System. Bioscience 64:570-580
Bose, Amitabha; Golowasch, Jorge; Guan, Yinzheng et al. (2014) The role of linear and voltage-dependent ionic currents in the generation of slow wave oscillations. J Comput Neurosci 37:229-42
Unal, Cagri T; Golowasch, Jorge P; Zaborszky, Laszlo (2012) Adult mouse basal forebrain harbors two distinct cholinergic populations defined by their electrophysiology. Front Behav Neurosci 6:21
Zhao, Shunbing; Golowasch, Jorge (2012) Ionic current correlations underlie the global tuning of large numbers of neuronal activity attributes. J Neurosci 32:13380-8
Zhang, Yili; Golowasch, Jorge (2011) Recovery of rhythmic activity in a central pattern generator: analysis of the role of neuromodulator and activity-dependent mechanisms. J Comput Neurosci 31:685-99
Zhao, Shunbing; Golowasch, Jorge; Nadim, Farzan (2010) Pacemaker neuron and network oscillations depend on a neuromodulator-regulated linear current. Front Behav Neurosci 4:21
Zhang, Yili; Khorkova, Olga; Rodriguez, Rosa et al. (2009) Activity and neuromodulatory input contribute to the recovery of rhythmic output after decentralization in a central pattern generator. J Neurophysiol 101:372-86
Golowasch, Jorge; Thomas, Gladis; Taylor, Adam L et al. (2009) Membrane capacitance measurements revisited: dependence of capacitance value on measurement method in nonisopotential neurons. J Neurophysiol 102:2161-75
Zhang, Yili; Golowasch, Jorge (2007) Modeling Recovery of Rhythmic Activity: Hypothesis for the role of a calcium pump. Neurocomputing 70:1657-1662

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