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Collagen VI (Col-VI) is an extracellular matrix protein primarily known for its bridging role in connective tissues that has been suggested to play a neuroprotective role. In the present study we report increased mRNA and protein expression of Col-VI in the hippocampus and cortex at a late stage of epileptogenesis in a post- status epilepticus (SE) model of epilepsy and in brain tissue from patients with epilepsy. We further present a novel finding that exposure of mouse hippocampal slices to Col-VI augments paired-pulse facilitation in Schaffer collateral-CA1 excitatory synapses indicating decreased release probability of glutamate. In line with this finding, lack of Col-VI expression in the knock-out mice show paired-pulse depression in these synapses, suggesting increased release probability of glutamate. In addition, we observed dynamic changes in Col-VI blood plasma levels in rats after Kainate-induced SE, and increased levels of Col-VI mRNA and protein in autopsy or postmortem brain of humans suffering from epilepsy. Thus, our data indicate that elevated levels of ColVI following seizures leads to attenuated glutamatergic transmission, ultimately resulting in less overall network excitability. Presumably, increased Col-VI may act as part of endogenous compensatory mechanism against enhanced excitability during epileptogenic processes in the hippocampus, and could be further investigated as a potential functional biomarker of epileptogenesis, and/or a novel target for therapeutic intervention. • Role of Collagen VI in Epilepsy: This study examines how Collagen VI affects synaptic transmission and its role in seizure-related excitability. • Increased Expression in Epilepsy Models: Collagen VI mRNA and protein levels are elevated in rodent epilepsy models and human epilepsy patients. • Synaptic Transmission Modulation: Col-VI in hippocampal slices reduces glutamate release, decreasing neuronal excitability. Knock-out mice show increased release. • Potential Compensatory Mechanism: Elevated Col-VI after seizures may act as a compensatory mechanism to reduce network excitability. • Future Directions: Further research on Col-VI's role in seizure modulation, including overexpression models and seizure parameter correlations. [ABSTRACT FROM AUTHOR]

Inputs to apical dendritic tufts have been considered to be crucial for associative learning, attention and similar ''feedback'' interactions and are located in neocortical layer Ia. Excitatory thalamic projections to apical tufts in layer Ia have been well characterized and their role in the cortical circuit has been emphasized. In addition, the neuropil and the extracellular matrix surrounding apical tufts are highly reactive to GABA and to the glycoprotein Reelin, respectively. Recently it has been shown that the GABA inhibition on apical dendrites can reduce the output of pyramidal cells in layer V, however, the origin of 89 % of the symmetric synapses in layer I still remains unknown. In the present study we have systematically analyzed the origin of the GABAergic neuropil in neocortical layer Ia in a qualitative and quantitative manner, and investigated the possible extrinsic origin of the rich extracellular Reelin content of the same layer. We show that the inhibitory inputs in a given spot in layer I come from cortical projections and arise mainly from Martinotti cells located directly under that same spot. Double bouquet and bipolar cells may also project to layer Ia although to a lesser extent and the external globus pallidus and zona incerta provide the remaining inhibitory inputs. Finally, our results suggest that Martinotti cells are also the main source of Reelin in layer Ia. The present data will help in the understanding of the cortical circuit and why it changes in pathological conditions. [ABSTRACT FROM AUTHOR]

Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal (‘perforant’) path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits. [ABSTRACT FROM AUTHOR]