Effects of lactate on the early visual cortex of non-human primates, investigated by pharmaco-MRI and neurochemical analysis

Pföstl, Veronika von; Li, Juan; Zaldívar, Daniel; Goense, Jozien; Zhang, Xiaozhe; Serr, Nadine; Logothetis, Nikos K.; Rauch, Alexander

doi:10.1016/j.neuroimage.2012.02.082

Cited by 14 publications

(12 citation statements)

References 33 publications

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“…Figure 1C shows the changes in the BOLD response over the course of the LDC injection. BOLD modulation in the predrug period was 2.5% 6 1.1%, which is typical for anesthetized monkeys at 7T [9][10][11]. During the drug infusion, we observed a significant reduction in the visually induced modulation (Figures 1C and 1D; MOD drug = 50% 6 5.3%; p = 0.034), which was sustained after the infusion was stopped (MOD post = 60% 6 4.2%; p = 0.05).…”

Section: Resultsmentioning

confidence: 56%

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

et al. 2014

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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.

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Section: Resultsmentioning

confidence: 56%

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

et al. 2014

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“…), and 2.5 ± 0.9 mmol/L (von Pföstl et al . ), led to an augmentation of the CBF response to visual stimuli.…”

Section: Resultsmentioning

confidence: 87%

The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review

Hollyer

Bordoni

Kousholt

et al. 2019

Journal of Neurochemistry

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Lactate's role in the brain is understood as a contributor to brain energy metabolism, but it may also regulate the cerebral microcirculation. The purpose of this systematic review was to evaluate evidence of lactate as a physiological effector within the normal cerebral microcirculation in reports ranging from in vitro experiments to in vivo studies in animals and humans. Following pre‐registration of a review protocol, we systematically searched the PubMed, EMBASE , and Cochrane databases for literature covering themes of ‘lactate’, ‘the brain’, and ‘microcirculation’. Abstracts were screened, and data extracted independently by two individuals. We excluded studies evaluating lactate in disease models. Twenty‐eight papers were identified, 18 of which were in vivo animal experiments (65%), four on human studies (14%), and six on in vitro or ex vivo experiments (21%). Approximately half of the papers identified lactate as an augmenter of the hyperemic response to functional activation by a visual stimulus or as an instigator of hyperemia in a dose‐dependent manner, without external stimulation. The mechanisms are likely to be coupled to NAD + / NADH redox state influencing the production of nitric oxide. Unfortunately, only 38% of these studies demonstrated any control for bias, which makes reliable generalizations of the conclusions insecure. This systematic review identifies that lactate may act as a dose‐dependent regulator of cerebral microcirculation by augmenting the hyperemic response to functional activation below 5 mmol/kg, and by initiating a hyperemic response above 5 mmol/kg. Open Science Badges This article has received a badge for * Pre‐registration * because it made the data publicly available. The data can be accessed at www.radboudumc.nl/getmedia/53625326-d1df-432c-980f-27c7c80d1a90/THollyer_lactate_protocol.aspx . The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/ .

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“…Accordingly, it has been convincingly shown that CBF response to an increase in neuronal activity is modulated by changes in the plasma lactate/pyruvate ratio in experimental animals ( Ido et al, 2001, 2004) and humans ( Mintun et al, 2004; Vlassenko et al, 2006). Accordingly, it has been recently shown that lactate indeed modulates the BOLD fMRI signal in the early visual cortex of non-human primates ( von Pfostl et al, 2012). These results and others ( Kasischke et al, 2004) support a direct metabolic (glycolytic) effect on CBF regulation and identify astrocytes as important players in the generation of neuroimaging signals.…”

Section: Metabolism Vs Neurotransmissionmentioning

confidence: 99%

Neurophysiological, metabolic and cellular compartments that drive neurovascular coupling and neuroimaging signals

Moreno

Jégo

Cruz

et al. 2013

Front. Neuroenergetics

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Complete understanding of the mechanisms that coordinate work and energy supply of the brain, the so called neurovascular coupling, is fundamental to interpreting brain energetics and their influence on neuronal coding strategies, but also to interpreting signals obtained from brain imaging techniques such as functional magnetic resonance imaging. Interactions between neuronal activity and cerebral blood flow regulation are largely compartmentalized. First, there exists a functional compartmentalization in which glutamatergic peri-synaptic activity and its electrophysiological events occur in close proximity to vascular responses. Second, the metabolic processes that fuel peri-synaptic activity are partially segregated between glycolytic and oxidative compartments. Finally, there is cellular segregation between astrocytic and neuronal compartments, which has potentially important implications on neurovascular coupling. Experimental data is progressively showing a tight interaction between the products of energy consumption and neurotransmission-driven signaling molecules that regulate blood flow. Here, we review some of these issues in light of recent findings with special attention to the neuron-glia interplay on the generation of neuroimaging signals.

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Effects of lactate on the early visual cortex of non-human primates, investigated by pharmaco-MRI and neurochemical analysis

Cited by 14 publications

References 33 publications

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

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

The evidence for the physiological effects of lactate on the cerebral microcirculation: a systematic review

Neurophysiological, metabolic and cellular compartments that drive neurovascular coupling and neuroimaging signals

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