2 results
Maternal separation with early weaning: A rodent model providing novel insights into neglect associated developmental deficits
- Becky C. Carlyle, Alvaro Duque, Robert R. Kitchen, Kelly A. Bordner, Daniel Coman, Eliza Doolittle, Xenophonios Papademetris, Fahmeed Hyder, Jane R. Taylor, Arthur A. Simen
-
- Journal:
- Development and Psychopathology / Volume 24 / Issue 4 / November 2012
- Published online by Cambridge University Press:
- 15 October 2012, pp. 1401-1416
-
- Article
- Export citation
-
Child neglect is the most prevalent form of child maltreatment in the United States, and poses a serious public health concern. Children who survive such episodes go on to experience long-lasting psychological and behavioral problems, including higher rates of post-traumatic stress disorder symptoms, depression, alcohol and drug abuse, attention-deficit/hyperactivity disorder, and cognitive deficits. To date, most research into the causes of these life-long problems has focused on well-established targets such as stress responsive systems, including the hypothalamus–pituitary–adrenal axis. Using the maternal separation and early weaning model, we have attempted to provide comprehensive molecular profiling of a model of early-life neglect in an organism amenable to genomic manipulation: the mouse. In this article, we report new findings generated with this model using chromatin immunoprecipitation sequencing, diffuse tensor magnetic resonance imaging, and behavioral analyses. We also review the validity of the maternal separation and early weaning model, which reflects behavioral deficits observed in neglected humans including hyperactivity, anxiety, and attentional deficits. Finally, we summarize the molecular characterization of these animals, including RNA profiling and label-free proteomics, which highlight protein translation and myelination as novel pathways of interest.
Biophysical basis of brain activity: implications for neuroimaging
- Robert G. Shulman, Fahmeed Hyder, Douglas L. Rothman
-
- Journal:
- Quarterly Reviews of Biophysics / Volume 35 / Issue 3 / August 2002
- Published online by Cambridge University Press:
- 21 January 2003, pp. 287-325
-
- Article
- Export citation
-
1. Summary 288
2. Introduction 288
3. Relationship between neuroenergetics and neurotransmitter flux 294
4. A model of coupling between neuroenergetics and neurotransmission 296
5. Relationship between neuroenergetics and neural spiking frequency 297
6. Comparison with previous electrophysiological and fMRI measurements 298
7. Contributions of non-oxidative energetics to a primarily oxidative brain 299
8. Possible explanation for non-oxidative energetics contributions 300
9. A model of total neuronal activity to support cerebral function 302
10. Implications for interpretation of fMRI studies 305
11. The restless brain 306
12. Acknowledgements 310
13. Appendix A. CMRO2by13C-MRS 310
14. Appendix B.Vcycand test of model 313
15. Appendix C. CMRO2by calibrated BOLD 316
16. Appendix D. Comparison of spiking activity of a neuronal ensemble with CMRO2318
17. References 320
In vivo13C magnetic resonance spectroscopy (MRS) studies of the brain have quantitatively assessed rates of glutamate–glutamine cycle (Vcyc) and glucose oxidation (CMRGlc(ox)) by detecting 13C label turnover from glucose to glutamate and glutamine. Contrary to expectations from in vitro and ex vivo studies, the in vivo13C-MRS results demonstrate that glutamate recycling is a major metabolic pathway, inseparable from its actions of neurotransmission. Furthermore, both in the awake human and in the anesthetized rat brain, Vcyc and CMRGlc(ox) are stoichiometrically related, where more than two thirds of the energy from glucose oxidation supports events associated with glutamate neurotransmission. The high energy consumption of the brain measured at rest and its quantitative relation to neurotransmission reflects a sizeable activity level for the resting brain. The high activity of the non-stimulated brain, as measured by cerebral metabolic rate of oxygen use (CMRO2), establishes a new neurophysiological basis of cerebral function that leads to reinterpreting functional imaging data because the large baseline signal is commonly discarded in cognitive neuroscience paradigms. Changes in energy consumption (ΔCMRO2%) can also be obtained from magnetic resonance imaging (MRI) experiments, using the blood oxygen level- dependent (BOLD) image contrast, provided that all the separate parameters contributing to the functional MRI (fMRI) signal are measured. The BOLD-derived ΔCMRO2% when compared with alterations in neuronal spiking rate (Δν%) during sensory stimulation in the rat reveals a stoichiometric relationship, in good agreement with 13C-MRS results. Hence fMRI when calibrated so as to provide ΔCMRO2% can provide high spatial resolution evaluation of neuronal activity. Our studies of quantitative measurements of changes in neuroenergetics and neurotransmission reveal that a stimulus does not provoke an arbitrary amount of activity in a localized region, rather a total level of activity is required where the increment is inversely related to the level of activity in the non-stimulated condition. These biophysical experiments have established relationships between energy consumption and neuronal activity that provide novel insights into the nature of brain function and the interpretation of fMRI data.