Metabolic and behavioral deficits following a routine surgical procedure in rats

Frumberg, David B.; Fernando, Marion S.; Lee, Dianne E.; Biegon, Anat; Schiffer, Wynne K.

doi:10.1016/j.brainres.2007.01.134

Cited by 26 publications

(24 citation statements)

References 44 publications

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“…A number of studies have examined the impact of a number of surgical procedures on brain function, however only two have explicitly examined whether cognitive processes including memory are adversely affected (11,12). Both these studies detected impairment in recognition memory in contrast to the current study.…”

Section: Comparison With Previous Behavioural Studiescontrasting

confidence: 54%

Cannula implantation into the lateral ventricle does not adversely affect recognition or spatial working memory

Seyer

Pham

Albiston

et al. 2016

Neuroscience Letters

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Indwelling cannulas are often used to deliver pharmacological agents into the lateral ventricles of the brain to study their effects on memory and learning, yet little is known about the possible adverse effects of the cannulation itself. In this study, the effect of implanting an indwelling cannula into the right lateral ventricle was examined with respect to cognitive function and tissue damage in rats. Specifically, the cannula passed through sections of the primary motor (M1) and somatosensory hind limb (S1HL) cortices. One week following implantation, rats were impaired on the rotarod task, implying a deficit in fine motor control, likely caused by the passage of the cannula through the aforementioned cortical regions. Importantly, neither spatial working nor recognition memory was adversely affected. Histological examination showed immune cell activation only in the area immediately surrounding the cannulation site and not spreading to other brain regions. Both GFAP and CD-11b mRNA expression was elevated in the area immediately surrounding the cannulation site, but not in the contralateral hemisphere or the hippocampus. Neither of the inflammatory cytokines, TNF-α or IL-6, were upregulated in any region. These results show that cannulation into the lateral ventricle does not impair cognition and indicates that nootropic agents delivered via this method are enhancing normal memory rather than rescuing deficits caused by the surgery procedure.

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Section: Comparison With Previous Behavioural Studiescontrasting

confidence: 54%

Cannula implantation into the lateral ventricle does not adversely affect recognition or spatial working memory

Seyer

Pham

Albiston

et al. 2016

Neuroscience Letters

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“…DREAMM is most suited for studying behavioral profiles generated from ensembles of neurons than those relevant to the activity of a single cell. Moreover, DREAMM does not rely on complex surgical practices (chronic indwelling cannulas), which induce significant decreases in brain activity and inflammatory responses as well as cognitive deficits (25,26). Since DREAMM is not limited to probing cellular activity, it could also be used to provide insights into ed i.p.…”

Section: Discussionmentioning

confidence: 99%

Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks

et al. 2013

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The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with μPET and [ 18 F]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy. We applied this strategy to evaluating changes in the brain associated with inhibition of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) of the nucleus accumbens shell (NAcSh), which have been implicated in neuropsychiatric disorders. DREAMM revealed discrete behavioral manifestations and concurrent engagement of distinct corticolimbic networks associated with dysregulation of Pdyn and Penk in MSNs of the NAcSh. Furthermore, distinct neuronal networks were recruited in awake versus anesthetized conditions. These data demonstrate that DREAMM is a highly sensitive, molecular, high-resolution quantitative imaging approach. IntroductionThe mammalian brain is a complex organ with billions of heterogeneous cells whose local and long-range functional connections regulate behavior and physiology. Traditional approaches used for mapping functional brain anatomy do not provide information on long-range, global (i.e., intact whole brain) circuits. Recently, optogenetics was coupled with in vivo functional MRI (fMRI) and allowed, for what we believe is the first time, assessment of functional anatomy of discrete cell types in living animals (1, 2). fMRI technology, however, relies on nonmolecular, indirect measures of neuronal activity (i.e., neurovascular coupling) and is limited in its applicability to anesthetized or immobilized animals. Importantly, a recent study showed that light delivery in the absence of optogenetic stimulation induced strong local fMRI responses in the stimulated site (3). To overcome these limitations, we combined designer receptor exclusively activated by designer drug (DREADD) technology (4), which allows remote in vivo control of cell-specific firing (5), together with behavioral imaging using μPET and [ 18 F]fluorodeoxyglucose (FDG) to measure regional brain glucose metabolism, which is a direct marker of brain function (6-9). This approach, termed DREADD-assisted metabolic mapping (DREAMM), was used to map functional brain anatomy associated with inhibiting the activity of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) in the medial nucleus accum-

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“…On the other hand, ntPET is non-invasive and can be performed on humans. The collateral effects of microdialysis on brain physiology have recently been questioned, particularly with regard to probe-induced damage to tissue integrity Tang et al, 2003), cerebral metabolism (Frumberg et al, 2007;Schiffer et al, 2006a), and animal behavior (Frumberg et al, 2007). These alterations will not be caused by ntPET.…”

Section: E Ntpet As a Complement To Microdialysismentioning

confidence: 99%

Estimating neurotransmitter kinetics with ntPET: A simulation study of temporal precision and effects of biased data

Normandin

Morris

2008

NeuroImage

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We recently introduced ntPET (neurotransmitter PET), an analysis technique which estimates the kinetics of stimulus-induced neurotransmitter (NT) release. Here, we evaluate two formulations of ntPET. The arterial (ART) approach measures the tracer input function (TIF) directly. The reference (REF) approach derives the TIF from reference region data. Arterial sampling is considered the gold standard in PET modeling but reference region approaches are preferred for reduced cost and complexity. If simulated PET data with unbiased TIFs were analyzed using ART or REF, temporal precision was better than three minutes provided NT concentration peaked less than 30 minutes into the scanning session. The consequences of biased TIFs or stimulus-induced changes in tracer delivery were also evaluated. ART TIFs were biased by the presence of uncorrected radiometabolites in the plasma whereas REF TIFs were biased by specific binding in the reference region. Simulated changes in tracer delivery emulated ethanol-induced blood flow alterations observed previously with PET (Volkow et al., 1988). ART performance deteriorated significantly if metabolites amounted to 50% of plasma radioactivity by 60 minutes. The accuracy and precision of REF were preserved even if the reference region contained 40% of the receptor density of the target region. Both methods were insensitive to blood flow alterations (proportional changes in K 1 and k 2 ). Our results suggest that PET data contain information -heretofore not extracted -about the timing of NT release. The REF formulation of ntPET proved to be robust to many plausible model violations and under most circumstances is an appropriate alternative to ART.

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Metabolic and behavioral deficits following a routine surgical procedure in rats

Cited by 26 publications

References 44 publications

Cannula implantation into the lateral ventricle does not adversely affect recognition or spatial working memory

Cannula implantation into the lateral ventricle does not adversely affect recognition or spatial working memory

Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks

Estimating neurotransmitter kinetics with ntPET: A simulation study of temporal precision and effects of biased data

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