Construction of simple, customised, brain-spanning, multi-channel, linear microelectrode arrays.

BACKGROUND: The construction of multichannel micro-electrode arrays (MEA) generally requires complex and expensive procedures. Here we describe a simple, cheap, flexible method of linear MEA construction. NEW METHOD: Our method allows manufacture of linear MEA (cross section ∼ 375 × 250 µm with 12 electrodes) of any desired length, with customized spacing of the electrode tips (down to a minimum spacing of 200 µm or less) to suit different needs and experiments. We describe the following steps: (1) set-up for MEA construction; (2) building of a construction jig; (3) building the reference, ground and optional electrical stimulation electrodes; (4) treatment of the main recording microwires; (5) soldering of the microwires to the main connector plug and arrangement of the microwires in a customizable array; and (6) testing of the MEA resistance and correct connections. Finally, we describe methods for quick surgical implantation of multiple MEAs and bipolar micro-stimulation electrodes for in vivo experiments in free-moving rats. RESULTS: We provide examples of multi-site local field potentials from prolonged recordings in awake and free-moving rodents, with recordings viable for months, as well as samples of electrical stimulation effects on cortical and hippocampal recordings. Hippocampal recordings showed clear phase reversal and amplitude changes across its layers. CONCLUSIONS: We briefly discuss how the arrays can support other forms of stimulation such as optogenetic probes.

Expression of CD40 Correlates Negatively with Overall and Progression-Free Survival of Low- and High-Grade Gliomas.

BACKGROUND: Low-grade gliomas (LGGs) are known to progress to glioblastoma (GBM), decreasing the chances of survival. The tumor necrosis factor receptor CD40 and its ligand CD40L have shown value as biomarkers for GBM. The present study evaluated the role of CD40/CD40L in LGG and GBM in differentiating isocitrate dehydrogenase (IDH) wild-type and IDH-mutant GBM. METHODS: The present study was based on patient-derived samples (74 grade II gliomas, 36 grade III gliomas, and 40 cases of GBM) and expression analysis using real-time polymerase chain reaction. Open-access data from The Cancer Genome Atlas (TCGA) and the strong cohorts of TCGA data sets "brain lower grade glioma" and "glioblastoma" were used to run the analysis on mRNA expression as a validation data set. RESULTS: We found that patients with LGG and CD40 overexpression experienced shorter progression-free survival (43 vs. 29 months; hazard ratio, 0.5715; P = 0.0262) and overall survival (116 vs. 54 months; hazard ratio, 0.3431; P < 0.0001). Consistently, relapsed grade II glioma showed greater CD40 expression compared with primary grade II glioma (P = 0.0028). Just as with LGG, CD40 was a negative marker for overall survival in GBM (12 vs. 10 months; hazard ratio, 0.5178; P = 0.0491). In this context, we found greater CD40 expression in IDH wild-type GBM than in IDH-mutant GBM. The data obtained from TCGA supported our findings, with similar results for PFS and OS in LGG and GBM. CD40L expression showed no correlation with the survival data. CONCLUSION: High CD40 expression showed a significant correlation with poor outcomes for both LGG and GBM and was overexpressed in IDH wild-type GBM.

Proximal perimeter encoding in the rat rostral thalamus.

Perimeters are an important part of the environment, delimiting its geometry. Here, we investigated how perimeters (vertical walls; vertical drops) affect neuronal responses in the rostral thalamus (the anteromedial and parataenial nuclei in particular). We found neurons whose firing patterns reflected the presence of walls and drops, irrespective of arena shape. Their firing patterns were stable across multiple sleep-wake cycles and were independent of ambient lighting conditions. Thus, rostral thalamic nuclei may participate in spatial representation by encoding the perimeters of environments.

Environmental enrichment increases prefrontal EEG power and synchrony with the hippocampus in rats with anterior thalamus lesions.

The anterior thalamic nuclei (ATN) are a major interface between the hippocampus and prefrontal cortex within an extended Papez circuit. Rat models suggest that the deficits caused by ATN damage, which is associated with "diencephalic amnesia", can be ameliorated by environmental enrichment (EE) through unknown mechanisms. We examined whether changes in theta rhythmicity within and between the hippocampus and prefrontal cortex are influenced by EE in rats with ATN lesions. Here, we show that ATN lesions and EE produced essentially opposed functional effects in terms of changes in rhythmicity between two consecutive trials when rats forage for chocolate hail. On the second trial, standard-housed rats with ATN lesions showed: (a) a clear reduction in prefrontal cortex experience-dependent power change in the theta band and in two adjacent bands; (b) little change in the theta band in hippocampal area CA1; and (c) only a modest overall reduction in experience-dependent power change at lower theta frequencies in the dentate gyrus. EE exposure prevented the decrease in prefrontal theta power in rats with ATN lesions, and in fact caused a clear increase in prefrontal cortex power across all bands. While ATN lesions did not reliably affect prefrontal-CA1 or prefrontal-dentate theta coherence, EE increased the coherence between prefrontal cortex and area CA1 in both the sham and ATN groups. Thus, EE increases functional connectivity between prefrontal cortex and hippocampus via pathways that bypass the ATN, and increases behaviorally dependent prefrontal rhythmicity. These EEG effects may contribute to improved learning and memory in the ATN-lesion model of diencephalic amnesia.

The persistence of long-term potentiation in the projection from ventral hippocampus to medial prefrontal cortex in awake rats.

A potentially vital pathway in the processing of spatial memory is the pathway from ventral hippocampus to medial prefrontal cortex (vHPC-mPFC). To assess long-term potentiation (LTP) induction and maintenance across days in this pathway, the effects of several induction paradigms were compared in awake, freely moving rats. Two different high-frequency stimulation (HFS) protocols generated LTP lasting no longer than 1 week. However, after delivering HFS on three consecutive days, LTP lasted an average of 20 days, due mainly to the greater initial induction. Thus the pathway does not require extensive multi-day stimulation to induce LTP, as for other intra-neocortical pathways, but also it does not exhibit the extremely long-lasting and stable LTP previously observed in area CA1 and the dentate gyrus. By using bilaterally placed stimulating and recording electrodes, we found that HFS in one vHPC generated responses and LTP in the contralateral mPFC, even when the ipsilateral mPFC was inactivated by CNQX. We attribute this crossed response to a polysynaptic pathway from the vHPC to the contralateral mPFC. Finally, we found that repeated overnight exposure to an enriched environment also potentiated the vHPC-mPFC response, but this too was a transient effect lasting < 9 days, declining to baseline even before the enriched environment treatment was completed. Overall, these findings are consistent with the view that potentiation of vHPC-mPFC pathway may play a key role in promoting the hippocampus-mPFC interplay that, over days, leads to long-term storage in the frontal cortex of memories that are independent of the hippocampus.

Anterior thalamic nuclei lesions and recovery of function: Relevance to cognitive thalamus.

Injury to the anterior thalamic nuclei (ATN) and their neural connections is the most consistent neuropathology associated with diencephalic amnesia. ATN lesions in rats produce memory impairments that support a key role for this region within an extended hippocampal system of complex overlapping neural connections. Environmental enrichment is a therapeutic tool that produces substantial, although incomplete, recovery of memory function after ATN lesions, even after the lesion-induced deficit has become established. Similarly, the neurotrophic agent cerebrolysin, also counters the negative effects of ATN lesions. ATN lesions substantially reduce c-Fos expression and spine density in the retrosplenial cortex, and reduce spine density on CA1 neurons; only the latter is reversed by enrichment. We discuss the implications of this evidence for the cognitive thalamus, with a proposal that there are genuine interactions among different but allied thalamo-cortical systems that go beyond a simple summation of their separate effects.