Variations in the temporal pattern of perforant pathway stimulation control the activity in the mesolimbic pathway

Helbing, Cornelia; Werner, Grit; Angenstein, Frank

doi:10.1016/j.neuroimage.2012.09.001

Cited by 15 publications

(14 citation statements)

References 27 publications

(32 reference statements)

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“…Increase of NAc cellular activity following stimulation of the fornix-fimbria or ventral subiculum in rat (Boeijinga et al, 1993; Boeijinga et al, 1990; Yang and Mogenson, 1984, 1985) and cat (Lopes da Silva et al, 1984) have been previously reported. These studies, in combination with previous fMRI studies in rats showing BOLD increase in NAc following main hippocampal afferent pathway stimulation, are in agreement with the present data (Helbing et al, 2013; Krautwald et al, 2015). The HP, VTA, and NAc have high intrinsic functional interconnectivity, which provides the framework for this interplay (Kahn and Shohamy, 2013).…”

Section: Discussionsupporting

confidence: 94%

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

et al. 2016

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Introduction Deep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. Methods A multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. Results Hemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. Conclusions The present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and that the medial limbic and corticolimbic circuits interact in a functional loop.

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Section: Discussionsupporting

confidence: 94%

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

et al. 2016

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“…septal nuclei and retrosplenial cortex), as well as in regions not receiving significant projections such as the contralateral hippocampus and insular cortex (Jay et al, 1989). These findings are consistent with previous reports of functional connectivity between the hippocampus and both cortical and subcortical limbic structures (Englot et al, 2008; Helbing et al, 2013; Ranganath et al, 2005). While other functional imaging studies using direct stimulation of the hippocampus have not reported widespread recruitment beyond the hippocampal formation (Abe et al, 2012; Angenstein et al, 2007; Canals et al, 2009), these studies also offer important additional insight into which hippocampal dynamics affect global brain circuitry.…”

Section: Discussionsupporting

confidence: 93%

Optogenetic fMRI reveals distinct, frequency-dependent networks recruited by dorsal and intermediate hippocampus stimulations

et al. 2015

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Although the connectivity of hippocampal circuits has been extensively studied, the way in which these connections give rise to large-scale dynamic network activity remains unknown. Here, we used optogenetic fMRI to visualize the brain network dynamics evoked by different frequencies of stimulation of two distinct neuronal populations within dorsal and intermediate hippocampus. Stimulation of excitatory cells in intermediate hippocampus caused widespread cortical and subcortical recruitment at high frequencies, whereas stimulation in dorsal hippocampus led to activity primarily restricted to hippocampus across all frequencies tested. Sustained hippocampal responses evoked during high-frequency stimulation of either location predicted seizure-like afterdischarges in video-EEG experiments, while the widespread activation evoked by high-frequency stimulation of intermediate hippocampus predicted behavioral seizures. A negative BOLD signal observed in dentate gyrus during dorsal, but not intermediate, hippocampus stimulation is proposed to underlie the mechanism for these differences. Collectively, our results provide insight into the dynamic function of hippocampal networks and their role in seizures.

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“…As previously observed, 11 repetitive electrical stimulations of the perforant pathway with continuous 100 Hz pulses induced significant BOLD responses in the entire HC formation, in the septum, in the NAcc, mPFC/ ACC and in the VTA/SN region (n ¼ 13, Figure 3, Table S1). Outside the HC formation stronger BOLD responses were induced after the second stimulation train, and thus repetitive trains were required to elicit maximal BOLD responses.…”

Section: Dopamine Receptor Activation Is Necessary For the Formation supporting

confidence: 79%

“…To study the influence of dopaminergic transmission on the BOLD signals in mPFC/ACC and NAcc two related perforant pathway stimulation protocols were applied: a continuous and a discontinuous 100 Hz pulse protocol. 11,17 Both protocols reliably induce BOLD responses in mPFC/ACC and NAcc, but differ in their ability to generate significant BOLD responses in the VTA/SN region. Only the continuous stimulation protocol triggered significant BOLD responses in the VTA/SN region.…”

Section: Resultsmentioning

confidence: 99%

The role of the mesolimbic dopamine system in the formation of blood-oxygen-level dependent responses in the medial prefrontal/anterior cingulate cortex during high-frequency stimulation of the rat perforant pathway

Helbing

Brocka

Scherf

et al. 2016

J Cereb Blood Flow Metab

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Several human functional magnetic resonance imaging studies point to an activation of the mesolimbic dopamine system during reward, addiction and learning. We previously found activation of the mesolimbic system in response to continuous but not to discontinuous perforant pathway stimulation in an experimental model that we now used to investigate the role of dopamine release for the formation of functional magnetic resonance imaging responses. The two stimulation protocols elicited blood-oxygen-level dependent responses in the medial prefrontal/anterior cingulate cortex and nucleus accumbens. Inhibition of dopamine D receptors abolished the formation of functional magnetic resonance imaging responses in the medial prefrontal/anterior cingulate cortex during continuous but not during discontinuous pulse stimulations, i.e. only when the mesolimbic system was activated. Direct electrical or optogenetic stimulation of the ventral tegmental area caused strong dopamine release but only electrical stimulation triggered significant blood-oxygen level-dependent responses in the medial prefrontal/anterior cingulate cortex and nucleus accumbens. These functional magnetic resonance imaging responses were not affected by the D receptor antagonist SCH23390 but reduced by the N-methyl-D-aspartate receptor antagonist MK801. Therefore, glutamatergic ventral tegmental area neurons are already sufficient to trigger blood-oxygen-level dependent responses in the medial prefrontal/anterior cingulate cortex and nucleus accumbens. Although dopamine release alone does not affect blood-oxygen-level dependent responses it can act as a switch, permitting the formation of blood-oxygen-level dependent responses.

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Variations in the temporal pattern of perforant pathway stimulation control the activity in the mesolimbic pathway

Cited by 15 publications

References 27 publications

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

Optogenetic fMRI reveals distinct, frequency-dependent networks recruited by dorsal and intermediate hippocampus stimulations

The role of the mesolimbic dopamine system in the formation of blood-oxygen-level dependent responses in the medial prefrontal/anterior cingulate cortex during high-frequency stimulation of the rat perforant pathway

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