Dopamine-Induced Dissociation of BOLD and Neural Activity in Macaque Visual Cortex

Abstract

Neuromodulators determine how neural circuits process information during cognitive states such as wakefulness, attention, learning, and memory. fMRI can provide insight into their function and dynamics, but their exact effect on BOLD responses remains unclear, limiting our ability to interpret the effects of changes in behavioral state using fMRI. Here, we investigated the effects of dopamine (DA) injections on neural responses and haemodynamic signals in macaque primary visual cortex (V1) using fMRI (7T) and intracortical electrophysiology. Aside from DA's involvement in diseases such as Parkinson's and schizophrenia, it also plays a role in visual perception. We mimicked DAergic neuromodulation by systemic injection of L-DOPA and Carbidopa (LDC) or by local application of DA in V1 and found that systemic application of LDC increased the signal-to-noise ratio (SNR) and amplitude of the visually evoked neural responses in V1. However, visually induced BOLD responses decreased, whereas cerebral blood flow (CBF) responses increased. This dissociation of BOLD and CBF suggests that dopamine increases energy metabolism by a disproportionate amount relative to the CBF response, causing the reduced BOLD response. Local application of DA in V1 had no effect on neural activity, suggesting that the dopaminergic effects are mediated by long-range interactions. The combination of BOLD-based and CBF-based fMRI can provide a signature of dopaminergic neuromodulation, indicating that the application of multimodal methods can improve our ability to distinguish sensory processing from neuromodulatory effects.

DOP-2 D2-Like Receptor Regulates UNC-7 Innexins to Attenuate Recurrent Sensory Motor Neurons during C. elegans Copulation

“…5B-D). Similar to previous studies (Starich et al, 2009;Yeh et al, 2009;Kawano et al, 2011), this reporter also expresses, in head ganglion neurons, several ventral chord neurons, and tail neurons of the hermaphrodite, in addition to few unreported pharyngeal neurons (I5, M2, I4, M3, and I1). Therefore, this broad expression pattern indicates that UNC-7 could electrically couple sex-specific muscles and/or neurons to modulate circuitry output.…”

“…Loss-of-function mutations in gap-junctions, such as UNC-7 and UNC-9, can affect chemical neurotransmission properties in C. elegans and vertebrate models (Yeh et al, 2009;Wang and Belousov, 2011). Thus, perturbing UNC-7(L) function with the A59T mutation could directly alter responses related to ACh, instead of DA signaling.…”

“…3B) are broadly expressed in all premotor and motor neurons (Altun et al, 2009;Starich et al, 2009;Yeh et al, 2009;Kawano et al, 2011). Additionally, posterior body wall muscles showed UNC-7 fluorescent immunolabeling (Yeh et al, 2009;Kawano et al, 2011). To determine which tissues UNC-7 and DOP-2 overlap, we assessed the reported UNC-7(L) and (S) expression pattern in the male.…”

“…DA neurons project into RNNs in cortical regions (Brozoski et al, 1979;Goldman-Rakic et al, 1989) to adjust cognitive tasks via D1-or D2-like receptors (Matsumoto and Takada, 2013;Haber, 2014). In primates, D1-like signaling amplifies prefrontal and occipital cortical RNNs to promote purposeful eye movements to visual targets (Noudoost and Moore, 2011;Zaldivar et al, 2014). In contrast, how D2-like signaling alters RNNЈs control on behavior remains unknown because the complex cortical connectivity presents a challenge for behavioral studies.…”

Aging and Parkinson's disease as functional models of temporal order perception

“…(This is likely relevant, even though we have excluded participants with poor vision from our study.) Recent studies also indicate that dopamine enhances, through its activity in the prefrontal cortex, responses to visual signals in areas V1 (Zaldivar, Rauch, Whittingstall, Logothetis, & Goense, 2014) and V4 (Noudoost & Moore, 2011) of the visual cortex. It also enhances the representation of visual stimuli in the prefrontal cortex itself, where perceptual decisions are made (Jacob, Ott, & Nieder, 2013).…”