@Article{ vonPfostlLZGZSLR2012,
title = {Effects of lactate on the early visual cortex of non-human primates, investigated by pharmaco-MRI and neurochemical analysis},
journal = {NeuroImage},
year = {2012},
month = {5},
volume = {61},
number = {1},
pages = {98–105},
abstract = {In contrast to the limited use of functional magnetic resonance imaging (fMRI) in clinical diagnostics, it is currently a mainstay of neuroimaging in clinical and basic brain research. However, its non-invasive use in combination with its high temporal and spatial resolution would make fMRI a perfect diagnostic tool. We are interested in whether a pharmacological challenge imposed on the brain can be reliably traced by the blood oxygen level-dependent (BOLD) signal and possibly further exploited for diagnostics. We have chosen a systemic challenge with lactate and pyruvate to test whether the physiological formation of these monocarboxylic acids contributes to the BOLD signal and can be detected using fMRI. This information is also of interest because lactate levels in the cerebrospinal fluid rise concomitantly with reduced vascular responsiveness of the brain during the progression of Alzheimer disease (AD). We studied the BOLD response after a low-dose lactate challenge and monitored the induced plasma lactate levels in anesthetized non-human primates. We observed reliable lactate-induced BOLD responses, which could be confirmed at population and individual level by their strong correlation with systemic lactate concentrations. Comparable BOLD effects where observed after a slow infusion of pyruvate. We show here that physiological changes in lactate and pyruvate levels are indeed reflected in the BOLD signal, and describe the technical prerequisites to reliably trace a lactate challenge using BOLD-fMRI.},
web_url = {http://www.sciencedirect.com/science/article/pii/S1053811912002698},
state = {published},
DOI = {10.1016/j.neuroimage.2012.02.082},
author = {von Pf\"ostl V{vpfoestl}{Department Physiology of Cognitive Processes}, Li J{juan}{Department Physiology of Cognitive Processes}, Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}, Goense J{jozien}{Department Physiology of Cognitive Processes}, Zhang X{xiaozhe}{Department Physiology of Cognitive Processes}, Serr N{nserr}{Department Physiology of Cognitive Processes}, Logothetis NK{nikos}{Department Physiology of Cognitive Processes} and Rauch A{arauch}{Department Physiology of Cognitive Processes}}
}

@Poster{ LiZvSZLR2011,
title = {Nicotinic modulation of the early visual system and its underlying neuronal and metabolic changes},
year = {2011},
month = {11},
volume = {41},
number = {864.17},
abstract = {In macaques, cholinergic subreceptors of nicotine (nAChRs) are predominantly found in the excitatory afferents of the primary visual cortex (V1, layer 4c) originating from the lateral geniculate nucleus (LGN). This strategic termination pattern allows nicotine to up regulate thalamocortical activity, while in parallel activity outside layer 4c can be down regulated by nicotinic effects on GABAergic inhibition. In addition to this gain-modulating role, nicotine has also distinct neuroprotective effects. Here, we have examined whether such neuroprotective effects could be at least partially explained by the gain modulation itself which tunes neuronal networks to a most efficient input-output mode with little other interferences. We investigated nicotinic effects (systemic: 0.2mg/kg) in V1 by neurophysiological recordings using multi-laminar probes and sampling of intracortical glutamate, GABA and glutamine by microdialysis in anesthetized non-human primates. Multi unit activity (MUA: 900-3200 Hz) and gamma (65-120 Hz) activity showed an improved signal-to-noise ratio (SNR) while theta activity (4-8Hz) was significantly reduced (p<0.5). The neurochemical analysis on the other hand showed increased concentrations of GABA (+40%) while glutamate (-60%) and glutamine levels (-50%) were reduced. Taken together nicotine shifts the ratio between glutamate and GABA clearly to GABA inducing inhibitory effects which reduce excitation and result in low glutamate levels. The decrease in excitatory neuronal activity is reflected in the reduced theta activity and the improved SNR in MUA and the gamma band resulting in an efficient input-output relation due to little excitatory interferences. The low levels of glutamine are most likely caused by the increased synthesis of GABA for which glutamine is a metabolic precursor. The neuroprotective effects of nicotine can be explained by the reduction of glutamate sparing neuronal networks from abundant excitatory activity resulting in excitotoxic effects by glutamate itself and other potentially toxic metabolites.},
web_url = {http://www.sfn.org/am2011/},
event_name = {41st Annual Meeting of the Society for Neuroscience (Neuroscience 2011)},
event_place = {Washington, DC, USA},
state = {published},
author = {Li J{juan}{Department Physiology of Cognitive Processes}, Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}, von Pf\"ostl V{vpfoestl}{Department Physiology of Cognitive Processes}, Serr N{nserr}{Department Physiology of Cognitive Processes}, Zhang X{xiaozhe}{Department Physiology of Cognitive Processes}, Logothetis NK{nikos}{Department Physiology of Cognitive Processes} and Rauch A{arauch}{Department Physiology of Cognitive Processes}}
}