Opto-fMRI analysis for exploring the neuronal connectivity of the hippocampal formation in rats

Abe, Yoshifumi; Sekino, Masaki; Terazono, Yasushi; Ohsaki, Hiroyuki; Fukazawa, Yugo; Sakai, Seiichiro; Yawo, Hiromu; Hisatsune, Tatsuhiro

doi:10.1016/j.neures.2012.08.007

Cited by 43 publications

(39 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results show reasonable anatomical correspondence to the existing opto-fMRI literature in some respects: both previous studies stimulating the HC 9,10 -which were, however, performed in rats -reported BOLD activation in the ipsilateral HC as the most prominent finding. As in our study, this was not restricted to the region directly around the site of stimulation, but extended to other hippocampal areas.…”

Section: Discussionsupporting

confidence: 90%

“…Cre-dependent recombinant AAV vectors were produced with AAV 1/2 coat proteins and purified with heparin columns to a final viral concentration of approx. 10 16 genome copies/mL. 27 Mice aged >8 weeks were anesthetized with isoflurane; 0.25 mL of purified virus was injected into the left dorsal HC (from bregma: posterior 2.2 mm, lateral 1.5 mm; ventral 1.5 mm from brain surface).…”

Section: Methods Animalsmentioning

confidence: 99%

See 1 more Smart Citation

Optogenetic fMRI in the mouse hippocampus: Hemodynamic response to brief glutamatergic stimuli

Lebhardt

Hohenberg

Weber‐Fahr

et al. 2015

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

The combination of optogenetics with functional magnetic resonance imaging is a promising tool to study the causal relationship between specific neuronal populations and global brain activity. We employed this technique to study the brain response to recruitment of glutamatergic neurons in the mouse hippocampus. The light-sensitive protein channelrhodopsin-2 was expressed in a-CamKII-positive glutamatergic neurons in the left hippocampus (N ¼ 10). Functional magnetic resonance imaging was performed during local laser stimulation, with stimulus duration of 1 second. The hemodynamic response to these stimuli was analyzed on a whole-brain level. In a secondary analysis, we examined the impact of the stimulation locus on the dorso-ventral axis within the hippocampal formation. The hemodynamic response in the mouse hippocampus had an earlier peak and a shorter duration compared to those observed in humans. Photostimulation was associated with significantly increased blood oxygen level-dependent signal in group statistics: bilaterally in the hippocampus, frontal lobe and septum, ipsilaterally in the nucleus accumbens and contralaterally in the striatum. More dorsal position of the laser fiber was associated with a stronger activation in projection regions (insular cortex and striatum). The characterization of brain-region-specific hemodynamic response functions may enable more precise interpretation of future functional magnetic resonance imaging experiments.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Methods Animalsmentioning

confidence: 99%

Optogenetic fMRI in the mouse hippocampus: Hemodynamic response to brief glutamatergic stimuli

Lebhardt

Hohenberg

Weber‐Fahr

et al. 2015

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…The most widely used approach for in vivo imaging of the effects of electrical or optogenetic stimulations in rodents is BOLD-fMRI (Angenstein et al, 2009;Lee et al, 2010;Desai et al, 2011;Kahn et al, 2011;Abe et al, 2012. ) This method, however, requires the animals to be anesthetized or restrained inside scanners severely limiting the range of behavioral paradigms that can be studied.…”

Section: Introductionmentioning

confidence: 99%

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice

et al. 2014

View full text Add to dashboard Cite

Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography.

show abstract

“…Similar opto-fMRI studies examined the hippocampal connectivity of anesthetized rats (Abe et al, 2012), the somatosensory system of awake mice (Desai et al, 2011), as well as the visual system in anesthetized primates (Gerits et al, 2012). In addition, opto-fMRI was used to investigate neurovascular coupling (Kahn et al, 2013; Scott and Murphy, 2012), and it revealed the linearity of optically-evoked BOLD responses (Kahn et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Mapping the functional network of medial prefrontal cortex by combining optogenetics and fMRI in awake rats

et al. 2015

View full text Add to dashboard Cite

The medial prefrontal cortex (mPFC) plays a critical role in multiple cognitive and limbic functions. Given its vital importance, investigating the function of individual mPFC circuits in animal models has provided critical insight into the neural basis underlying different behaviors and psychiatric conditions. However, our knowledge regarding the mPFC whole-brain network stays largely at the anatomical level, while the functional network of mPFC, which can be dynamic in different conditions or following manipulations, remains elusive especially in awake rodents. Here we combined optogenetic stimulation and functional magnetic resonance imaging (opto-fMRI) to reveal the network of brain regions functionally activated by mPFC outputs in awake rodents. Our data showed significant increases in blood-oxygenation-level dependent (BOLD) signals in prefrontal, striatal and limbic regions when mPFC was optically stimulated. This activation pattern was robust, reproducible, and did not depend on the stimulation period in awake rats. BOLD signals, however, were substantially reduced when animals were anesthetized. In addition, regional brain activation showing increased BOLD signals during mPFC stimulation was corroborated by electrophysiological recordings. These results expand the applicability of the opto-fMRI approach from sensorimotor processing to cognition-related networks in awake rodents. Importantly, it may help elucidate the circuit mechanisms underlying numerous mPFC-related functions and behaviors that need to be assessed in the awake state.

show abstract

Opto-fMRI analysis for exploring the neuronal connectivity of the hippocampal formation in rats

Cited by 43 publications

References 17 publications

Optogenetic fMRI in the mouse hippocampus: Hemodynamic response to brief glutamatergic stimuli

Optogenetic fMRI in the mouse hippocampus: Hemodynamic response to brief glutamatergic stimuli

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice

Mapping the functional network of medial prefrontal cortex by combining optogenetics and fMRI in awake rats

Contact Info

Product

Resources

About