Mapping the brain-wide network effects by optogenetic activation of the corpus callosum

Abstract

words) 36The optogenetically driven manipulation of circuit-specific activity enabled functional causality studies in animals, 37 but its global effect on the brain is rarely reported. Here, we applied simultaneous fMRI with calcium recording to 38 map brain-wide activity by optogenetic activation of fibers running in one orientation along the corpus callosum(CC) 39 connecting the barrel cortex(BC). Robust positive BOLD signals were detected in the ipsilateral BC due to 40 antidromic activity, which spread to ipsilateral motor cortex(MC) and posterior thalamus(PO). In the orthodromic 41 target (contralateral barrel cortex), positive BOLD signals were reliably evoked by 2Hz light pulses, whereas 40Hz 42 light pulses led to a reversed sign of BOLD -indicative of CC-mediated inhibition. This presumed optogenetic CC-43 mediated inhibition was further elucidated by pairing light with peripheral whisker stimulation at varied inter-44 stimulus intervals. Whisker induced positive BOLD, and calcium signals were reduced at inter-stimulus intervals 45 of 50/100ms. The calcium-amplitude modulation (AM)-based correlation with whole-brain fMRI signal revealed 46 that the inhibitory effects spread to contralateral BC as well as ipsilateral MC and PO. This work raises the need of 47 ensure the activation of neuronal ensembles of interest [1][2][3][4]. Optogenetic tools have revolutionized the strategy to 51 perturb or manipulate the behavior of animals [5][6][7][8]. To interpret the linkage of the brain function to specific 52 behavioral readout relies on the assumed circuit-specific manipulation through in vivo optogenetic activation [9-53 12]. Optogenetic activation of numerous brain sites and defined neuronal populations in animals has been very 54 successful to modulate behavior. However, there is a lack of systematic mapping of the result of specific modulation 55 on brain-wide network activity, which may relay and affect the proposed link between function and behavior. 56Progress in this direction depends on the combined application of methods to explore large scale brain dynamics as 57 well [13][14][15][16]. One useful method for this purpose is functional magnetic resonance imaging (fMRI) , which has 58 been successfully combined with optogenetics [17][18][19][20][21][22]. We use here a method that adds GCaMP-mediated calcium 59 recordings through an optical fiber for concurrent fMRI and neuronal calcium signal recording [23][24][25][26][27]. This multi-60 modal cross-scale brain dynamic mapping scheme allows elucidating network activity upon circuit-specific 61 optogenetic activation on the specific target level as well as across large brain regions [19,[23][24][25][27][28][29]. 62Corpus callosum (CC), the major neural fiber bundles connecting the two hemispheres, plays a critical role to 63 mediate the interhemispheric cortico-cortical connections [30][31][32]. Despite the highly-correlated structural 64 anomalies of the CC with a wide range of disorders, e.g., schizophrenia [33, 34], autism [35, 36], epilepsy [37, 3...

Focal fMRI signal enhancement with implantable inductively coupled detectors

“…3c ) were displayed to repsent the layer-specific hemodynamic responses. Interestingly, the evoked BOLD signal in the left FP-S1 ipsilateral to the stimulated forepaw showed salient post-stimulus undershoots in L2/3 and L5, indicating a transcallosal projection-mediated interhemispheric inhibition (Karayannis, Huerta-Ocampo et al 2007, Palmer, Schulz et al 2012, Chen, Sobczak et al 2020). Also, the laminar-specific tSNR with ICD showed up to 3-fold SNR increase over the bilateral line-scanning fMRI signals detected only with surface coil ( Fig.…”

“…However, given the implantation of optical fiber, it remains challenging to apply the advanced cryoprobe (Darrasse and Ginefri 2003, Baltes, Radzwill et al 2009) or multi-array radio frequency (RF) coils (Roemer, Edelstein et al 1990, Gareis, Wichmann et al 2007) for focal signal enhancement. Also, even with the surface coil designed to accommodate optical fiber implantation (Yu, He et al 2016, Chen, Sobczak et al 2019, Chen, Sobczak et al 2020), the adhesive surgical material used to fix the fiber at the skull creates a large distance between the surface coil and brain regions, which further restricts the acquisition of laminar fMRI signal with sufficient SNR.…”

Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI

“…Also, the negative BOLD signal was maintained with longer spreading function than typical positive BOLD responses excluded the only contribution from CBV and CBF effects, suggesting a sustained corticocortical post-synaptic inhibition ( Fig. S1 A ) (47,68). It is also noteworthy that the negative BOLD group (group 2) shows the salient biphasic HRF of the positive BOLD, of which the post-stimulus undershoot may be also caused by the decreased neuronal activity (43).…”

Laminar-specific interhemispheric connectivity mapping with bilateral line-scanning fMRI

“…3C and 4C ). Also, callosal circuit-specific optogenetic stimulation increased the power of the gamma frequency in L2/3 and L5 neurons [88], and mediated unique BOLD response patterns through ortho-and antidromic projections [89]. A future study to combine the callosal circuit-specific optogenetic stimulation with BiLS will further elucidate the causal relationship.…”