fMRI Used to Identify Neuronal Networks Activated by VTA or Hippocampal CA3 Stimulation

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Functional magnetic resonance (fMRI) imaging can provide insight into hemodynamic shifts that occur in blood, including blood volume, flow, and oxygenation. The technique can also be used to map neuronal networks and detect synchronized activities within the brain.

The reason why fMRI is commonly utilized to map functionally connected brain regions is that when a specific region fuels the activity in another region, the intensities of the fMRI signals will develop in a similar manner. However, there is discussion within the scientific community over whether blood oxygen level dependent (BOLD) fMRI can identify current functional connectivities.

One potential approach is to electrically stimulate one region of the brain while attempting to identify changes in stimulus BOLD signal intensities in the regions that receive projections from the region that was previously activated.

In a study published by Scherf T et al, researchers used fMRI to detect networks within the brain that are “activated” via electrical stimulation.5 This electrical stimulation either occurs through the VTA or hippocampal CA3.

It should be noted that the medial prefrontal cortex region receives glutamatergic, dopaminergic, and GABAergic projections for the ventral tegmental area (VTA).1,2 Glutamatergic transmission controls BOLD responses in the medial prefrontal cortex and anterior cingulum regions during short, high-frequency stimulating pulses to the VTA and prevents the formation of BOLD responses by a NMDA receptor antagonist.3,4

Also, it should be assumed that combined stimulations of the two structures may result in BOLD responses in common neuronal network areas. Specifically, an additive response might occur when a single target region receives excitatory inputs from two different brain structures.

In the study, researchers found that stimulation of either the VTA or the hippocampal CA3 resulted in significant BOLD responses in common brain structures, including the right and left hippocampus as well as the septum. Additional BOLD responses were noted in the medial prefrontal cortex and striatum during VTA stimulation.

Researchers used Wistar rats for the study. Using a stimulus generator, electrophysiological responses were evoked and recorded. All signals were digitally transferred to an analogue-to-digital interface.

In order to provide in-depth observation of the brain stimulation used in this study, researchers relied on a highly sophisticated assemblage of magnetic resonance imaging (MRI) tools. The MRI performed in this study was conducted on a Bruker BioSpec 47/20 scanner. Bruker’s BioSpec MRI platform provides high spatial resolution in vivo via CryoProbe™ technology, providing clear views at the cellular and molecular level. A Bruker BioSpin gradient system was also used with the BioSpec.

Additionally, a 50-mm Litzcage animal imaging system provided signal reception and radio frequency excitation. Exactly 8 horizontal T2-weighted spin-echo images provided rapid collection of relaxation-enhanced sequence for anatomical images.

Researchers combined the electrophysiological and fMRI experiments into three stimulation blocks, each containing identical stimulation trains. Total time for the combined session was approximately 35 minutes.

The findings showed that VTA electrical stimulation caused a substantial release in dopamine in target regions of the dopaminergic mesolimbic pathway, in turn causing a BOLD response. In addition to this finding, researchers also showed that with the use of low-frequency pulses at 2 Hz for stimulation of the left hippocampus, there was a reduction in BOLD responses in the medial prefrontal cortex and anterior cingulum regions.

There was an additional incoming excitatory (glutamatergic) input, a somewhat surprising finding from the study. This incoming excitatory input slightly degrades a BOLD response formation in the medial prefrontal cortex and anterior cingulum regions and exerts potential consequences for the comprehension of functional connectivities that result from correlating changes of BOLD signal intensities.

The researchers of this study also show that the left hippocampus and the VTA were either concurrently or separately stimulated. Both brain structures extend to different and common target regions, and combined stimulation may cause different activation patterns compared with only one structure receiving stimulation.


  1. Fields HL, Hjelmstad GO, Margolis EB, Nicola SM. Ventral tegmental area neurons in learned appetitive behavior and positive reinforcement. Annu Rev Neurosci. 2007;30:289-316.
  2. Lavin A, Nogueira L, Lapish CC, et al. Mesocortical dopamine neurons operate in distinct temporal domains using multimodal signaling. J Neurosci. 2005;25(20):5013-5023.
  3. Morales M, Root DH. Glutamate neurons within the midbrain dopamine regions. Neuroscience. 2014;282:60-8.
  4. Taylor SR, Badurek S, Dileone RJ, et al. GABAergic and glutamatergic efferents of the mouse ventral tegmental area. J Comp Neurol. 2014;522(14):3308-3334.
  5. Scherf T, Angenstein F. Hippocampal CA3 activation alleviates fMRI-BOLD responses in the rat prefrontal cortex induced by electrical VTA stimulation. PLoS One. 2017;12(2):e0172926.

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Last updated: Mar 11, 2022 at 1:57 AM


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