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=c-Fos Protein=
The immediate early gene product c-Fos is commonly used to map neural structures that are activated by the unconditioned and conditioned stimuli in CTA paradigms [Refs]. The c-Fos protein is expressed at a very low constituitive levels in many brain structures. Following US or CS stimulation of the animal, however, transynaptic activation of second messenger cascades causes the rapid but transient synthesis of c-Fos protein within 30 -180min. The c-Fos protein is easily visualized by immunohistochemistry; because c-Fos is a transcription factor, its labeling is discretely localized within cell nuclei. Thus, the presence of c-Fos after stimulation in a central relay implies direct or indirect activation of the relay by the stimulus. Quantification of the number of c-Fos positive cells provides a measure of response magnitude.
=c-Fos Expression as a Correlate of CTA Expression=
=c-Fos Expression as a Correlate of CTA Expression=
There are only a few scattered reports of neuronal activity correlated with CTA acquisition and expression. Shifts in the electrophysiological response of neurons to a standard gustatory stimulus after CTA acquisition in the NTS (Chang and Scott 1984), PBN (DiLorenzo 1985), amygdala(Yamamoto, Shimura et al. 1991), cortex (Yamamoto 1989), or elsewhere(Brozek, Buresova et al. 1974; Buresova, Aleksanyan et al. 1979) have been reported. Acetylcholine release in the n. accumbens is altered by CTA acquisition (Mark, Rada et al. 1992), and NMDA receptor phosphorylation increases in the gustatory cortex (Rosenblum, Berman et al. 1997). None of these neuronal correlates of CTA expression have been systematically characterized.
There are only a few scattered reports of neuronal activity correlated with CTA acquisition and expression. Shifts in the electrophysiological response of neurons to a standard gustatory stimulus after CTA acquisition in the NTS (Chang and Scott 1984), PBN (DiLorenzo 1985), amygdala(Yamamoto, Shimura et al. 1991), cortex (Yamamoto 1989), or elsewhere(Brozek, Buresova et al. 1974; Buresova, Aleksanyan et al. 1979) have been reported. Acetylcholine release in the n. accumbens is altered by CTA acquisition (Mark, Rada et al. 1992), and NMDA receptor phosphorylation increases in the gustatory cortex (Rosenblum, Berman et al. 1997). None of these neuronal correlates of CTA expression have been systematically characterized.
As a marker of neural activity after magnetic field stimulation, c-Fos offers another advantage
As a marker of neural activity after magnetic field stimulation, c-Fos offers another advantage
c-Fos is a delayed marker of brain activation. The same synaptic activity and intracellular cascades that mediate the acute processes of neuronal activity and behavior at the time of stimulation may also initiate the slower processes of immediate-early gene activation and protein synthesis. Activation of the c-Fos gene by a sensory stimulus results in c-Fos protein synthesis within 1h [54]. Because c-Fos is visualized 1 h after stimulation, there will be no interference of the magnet apparatus or MF stimulus with the visualization procedure.
6. c-Fos is a delayed marker of brain activation. The same synaptic activity and intracellular cascades that mediate the acute processes of neuronal activity and behavior at the time of stimulation may also initiate the slower processes of immediate-early gene activation and protein synthesis. Activation of the c-Fos gene by a sensory stimulus results in c-Fos protein synthesis within 1h [54]. Because c-Fos is visualized 1 h after stimulation, there will be no interference of the magnet apparatus or MF stimulus with the visualization procedure.
=Disadvantages of c-Fos=
=Disadvantages of c-Fos=
c-Fos expression also has disadvantages. It is a postmortem technique, so the same rat cannot be repeatedly tested. Also, only a subset of activated neurons may be visualized, because some cells do not express c-Fos when activated. Although there are other ways to record or visualize neural activity that avoid these problems, most are impractical when applied to high MFs. Electrophysiological recordings using surface or indwelling metallic electrodes are confounded either by magnetic attraction or by induced currents. Functional MRI, in addition to having relatively low-resolution in small animals, is obviously confounded by the presence of the MF if the field itself is inducing neuronal activity. Other methods of measuring brain activity, such as brain imaging by PET or voltage-sensitive dyes, or neurotransmitter release by microdialysis, would be prohibitively cumbersome to conduct within the confines of the magnet’s bore.
c-Fos expression also has disadvantages. It is a postmortem technique, so the same rat cannot be repeatedly tested. Also, only a subset of activated neurons may be visualized, because some cells do not express c-Fos when activated. Although there are other ways to record or visualize neural activity that avoid these problems, most are impractical when applied to high MFs. Electrophysiological recordings using surface or indwelling metallic electrodes are confounded either by magnetic attraction or by induced currents. Functional MRI, in addition to having relatively low-resolution in small animals, is obviously confounded by the presence of the MF if the field itself is inducing neuronal activity. Other methods of measuring brain activity, such as brain imaging by PET or voltage-sensitive dyes, or neurotransmitter release by microdialysis, would be prohibitively cumbersome to conduct within the confines of the magnet’s bore.