Cortical mechanisms of sensory learning and object recognition

Learning about the world through our senses constrains our ability to recognise our surroundings. Experience shapes perception. What is the neural basis for object recognition and how are learning-induced changes in recognition manifested in neural populations? We consider first the location of neurons that appear to be critical for object recognition, before describing what is known about their function. Two complementary processes of object recognition are considered: discrimination among diagnostic object features and generalization across non-diagnostic features. Neural plasticity appears to underlie the development of discrimination and generalization for a given set of features, though tracking these changes directly over the course of learning has remained an elusive task

Wo unser Gehirn das zusammenführt, was gehört und gefühlt wird: Forschungsbericht 2005 Max-Planck-Institut für biologische Kybernetik

New results demonstrate that those regions of the brain uniquely devoted to the processing of a single sense are rarer than classically thought. Instead, most of the brain is concerned with merging information across senses and creating a coherent percept

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) offers the possibility to generate longitudinal maps of brain activity in unrestrained and behaving animals. However, Mn2+ is a metabolic toxin and a competitive inhibitor for Ca2+, and therefore, a yet unsolved question in MEMRI studies is whether the concentrations of metal ion used may alter brain physiology. In the present work we have investigated the behavioral, electrophysiological and histopathological consequences of MnCl2 administration at concentrations and dosage protocols regularly used in MEMRI. Three groups of animals were sc injected with saline, 0.1 and 0.5 mmol/kg MnCl2, respectively. In vivo electrophysiological recordings in the hippocampal formation revealed a mild but detectable decrease in both excitatory postsynaptic potentials (EPSP) and population spike (PS) amplitude under the highest MnCl2 dose. The EPSP to PS ratio was preserved at control levels, indicating that neuronal excitability was not affected. Experiments of pair pulse facilitation demonstrated a dose dependent increase in the potentiation of the second pulse, suggesting presynaptic Ca2+ competition as the mechanism for the decreased neuronal response. Tetanization of the perforant path induced a long-term potentiation of synaptic transmission that was comparable in all groups, regardless of treatment. Accordingly, the choice accuracy tested on a hippocampal-dependent learning task was not affected. However, the response latency in the same task was largely increased in the group receiving 0.5 mmol/kg of MnCl2. Immunohistological examination of the hippocampus at the end of the experiments revealed no sign of neuronal toxicity or glial reaction. Although we show that MEMRI at 0.1 mmol/Kg MnCl2 may be safely applied to the study of cognitive networks, a detailed assessment of toxicity is strongly recommended for each particular study and Mn2+ administration protocol

Perfusion-based functional imaging in the monkey brain at 7T: investigations of CASL parameters

Perfusion-based imaging in the monkey primary visual cortex was performed at 7 T applying continuous arterial spin labeling (CASL). Increased perfusion sensitivity and SNR at high magnetic field (due to larger T1) was further optimized using a custom-made three-coil setup with a separate neck labeling coil. We investigated the labeling parameters to obtain relative fCBF changes in the anaesthetized monkey. We report excellent functional activation of striate cortex at high resolution of 0.75x0.9mm2 in-plane. Interestingly, the optimal parameter set for obtaining highest signal changes of rCBF are different from the reported values for imaging gray matter CBF

Continuous arterial spin labeling (CASL) in the monkey brain at high magnetic field using a three-coil approach

CASL experiments in the monkey brain were performed at 4.7 T and 7 T using a separate labeling coil. Increased sensitivity and SNR were achieved by a custom-made three-coil setup and high magnetic field with its increased T1. We report the development and optimization of the setup and first experiments in the monkey (macaca mulatta). Parameters for continuous labeling (label power, label duration, post label delay) were optimized to measure gray matter rCBF and fCBF changes, reporting excellent multi-slice coverage at high resolution of 0.75 – 1 mm in-plane

Region and volume dependencies in spectral linewidth assessed by 1H 2D chemical shift imaging in the monkey brain at 7T

High magnetic fields increase the sensitivity and spectral dispersion in MR spectroscopy. In contrast, spectral peaks are broadened in vivo at higher field strength due to stronger susceptibility-induced effects. Strategies to minimize the spectral linewidth are therefore of critical importance. In the present study, 1H 2D chemical shift imaging (CSI) at short echo time was performed in the macaque monkey brain at 7 T. Dependencies of spectral linewidth on the CSI voxel size were determined by data reconstruction at different spatial resolution. An overall linewidth narrowing at increased spatial resolution is shown and regional differences are demonstrated

Functionalized azamacrocyclic compounds as Ca2+ sensitive contrast agents for MR imaging

The ability to non-invasively observe changes in Ca2+ concentration is important for neuroscience. We have therefore developed a series of gadolinium chelate complexes based on DO3A (Scheme 1), which is hypothesized to change relaxivity in magnetic resonance experiments dynamically with Ca2+ concentration. Different lengths of the phosphonate side chains are expected to lead to different binding constants of the phosphonate - gadolinium bonds. The latter property can be exploited for fine-tuning the sensitivity of the agent to calcium ion concentration

Azamacrocyclic Ca2+ Sensitive Contrast Agents for MR Imaging

As calcium plays an important role in regulating a great variety of neuronal processes, many efforts are already made to generate gadolinium complexes that can act as a calcium-sensors in MRI.1 We developed a series of the DO3A-based macrocyclic and bismacrocyclic gadolinium chelates, bearing phosphonate groups as an additional coordination sites. These complexes are hypothesized to change the MRI contrast dynamically with Ca2+ concentration. Different lengths of the phosphonate side chains are exploited for fine-tuning the sensitivity of the agent to calcium ion concentration

Quantitative aspects of the microvascular system in macaque visual cortex

The basic principle of the most frequently used functional neuroimaging methods is the brain’s local dynamic regulation of blood flow. For a correct interpretation of neuroimaging results the structural and functional neurovascular coupling underlying this regulation must be well understood. Here we report quantitative anatomical data of the microvasculature in the macaque visual cortex. Formalin-fixed frozen sections of 4 animals (M. mulatta) were processed for double fluorescence immunohistochemistry. Sections were incubated with anti-collagen type IV and DAPI to stain for vessels and cell nuclei. In one additional animal, the anti-collagen procedure was combined with cytochrome oxidase staining in V1. The length density (LD), surface density (SD), volume fraction (VF) and diameter (D) of the vessels were stereologically determined. Furthermore, synchrotron-based computed tomographies (SRCT) of formalin-fixed and barium sulfate-perfused brain samples from another 2 animals were used to corroborate the histological results. In V1, the vascular density was highest in layer IVc- (LD 674.7 mm/mm3, SD 15.2 mm2/mm3, VF 2.6 , D 7.2 microns) and lowest in layer I (LD 461.5 mm/mm3, SD 10.9 mm2/mm3, VF 1.9 , D 7.5 microns). In all extrastriate visual areas analyzed (V2, V3, V4, V5), the vascular density was generally lower, and the difference between layer IV and the remaining layers was less prominent when compared to V1. These density values were similar compared to the ones tomographically obtained from SRCT. The vascular density in cytochrome oxidase rich blobs in V1 was 14 higher as compared to the interblob region. In summary, V1 is different from all extrastriate areas analyzed with respect to the laminar vessel distribution and overall vascular density. Differences between extrastriate areas were negligible. The overall vascular volume fraction in visual cortex derived from immunostaining was approximately 2 , a value that was well reproduced by the SRCT

In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing

One of the main problems in systems biology is to obtain information on signal processing between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge its applicability. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. In the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to produce detectable contrast and reliable connectivity maps. Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps. The somatosensory cortex of male SD rats was stereotaxically injected with different Mn2+-containing solutions. Total amount of injected Mn2+ ranged between 1 and 16 nmol and the injected volumes between 10 and 80 nL. Osmolarity and pH effects were investigated injecting pH buffered solutions of Mn2+ (pH 7.3 in Tris-HCl buffer vs. 5.5 in H2O) at different concentration (0.05, 0.1 and 0.8 M MnCl2). Same amounts of Mn2+ (8nmol) delivered to the tissue at different infusion rates were also compared. Following the injection, T1-weighted MR imaging (250 mm isotropic resolution) was performed in a 7T scanner at different time points. Fifteen days after the injection animals were sacrificed and brains processed for histology. Nissl staining as well as GFAP and NeuN immunohistochemistry (selective staining for astrocytes and neurons, respectively) were performed in the brain sections to examine cellular toxicity. All injections produced connectivity maps consistent with the known anterograde projections of SI cortex based on classical neuronal tract-tracing techniques. Our results show that pH buffered solution improve the effectiveness of MEMRI, increasing T1 contrast in the projection sites. In addition, injections of pH buffered and isotonic solutions of 50 and 100 mM MnCl2 yielded more extensive connectivity maps, in particular, ipsiand contra-lateral corticocortical connections were evident in all animal injected with those solutions but not with the more usual MEMRI protocol (0.8M MnCl2 in H2O). Hypertonic and non-buffered solutions containing 8nmol Mn2+ resulted in neuronal death and astrogliosis in extensive areas around the injection point. In sharp contrast, no neuronal toxicity was observed with injections containing up to 8nmol of Mn2+ in isotonic solutions of up to 100 mM MnCl2 and pH 7.3. Slow infusion rates demonstrated also to be advantageous and permitted application of larger amounts of Mn2+ without toxic effects, resulting in better T1 contrast in the low density projection fields. Any sign of toxicity was observed in any condition in the projection fields. We conclude that refined protocols for MEMRI improve the quality and extension of connectivity maps and preserves tissue viability, assuring the application of this technique in longitudinal experiments