Slow GABAA mediated synaptic transmission in rat visual cortex

<p>Abstract</p> <p>Background</p> <p>Previous reports of inhibition in the neocortex suggest that inhibition is mediated predominantly through GABA_Areceptors exhibiting fast kinetics. Within the hippocampus, it has been shown that GABA_Aresponses can take the form of either fast or slow response kinetics. Our findings indicate, for the first time, that the neocortex displays synaptic responses with slow GABA_Areceptor mediated inhibitory postsynaptic currents (IPSCs). These IPSCs are kinetically and pharmacologically similar to responses found in the hippocampus, although the anatomical specificity of evoked responses is unique from hippocampus. Spontaneous slow GABA_AIPSCs were recorded from both pyramidal and inhibitory neurons in rat visual cortex.</p> <p>Results</p> <p>GABA_Aslow IPSCs were significantly different from fast responses with respect to rise times and decay time constants, but not amplitudes. Spontaneously occurring GABA_Aslow IPSCs were nearly 100 times less frequent than fast sIPSCs and both were completely abolished by the chloride channel blocker, picrotoxin. The GABA_Asubunit-specific antagonist, furosemide, depressed spontaneous and evoked GABA_Afast IPSCs, but not slow GABA_A-mediated IPSCs. Anatomical specificity was evident using minimal stimulation: IPSCs with slow kinetics were evoked predominantly through stimulation of layer 1/2 apical dendritic zones of layer 4 pyramidal neurons and across their basal dendrites, while GABA_Afast IPSCs were evoked through stimulation throughout the dendritic arborization. Many evoked IPSCs were also composed of a combination of fast and slow IPSC components.</p> <p>Conclusion</p> <p>GABA_Aslow IPSCs displayed durations that were approximately 4 fold longer than typical GABA_Afast IPSCs, but shorter than GABA_B-mediated inhibition. The anatomical and pharmacological specificity of evoked slow IPSCs suggests a unique origin of synaptic input. Incorporating GABA_Aslow IPSCs into computational models of cortical function will help improve our understanding of cortical information processing.</p

Laminar and Dorsoventral Molecular Organization of the Medial Entorhinal Cortex Revealed by Large-scale Anatomical Analysis of Gene Expression

Neural circuits in the medial entorhinal cortex (MEC) encode an animal's position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations

The entorhinal cortex of Megachiroptera: a comparative study of Wahlberg's epauletted fruit bat and the straw-coloured fruit bat

This study describes the organisation of the entorhinal cortex of the Megachiroptera, Strawcoloured fruit bat and Wahlberg’s epauletted fruit bat. Using Nissl and Timm stains, parvalbumin and SMI-32 immunohistochemistry, we identified 5 fields within the medial(MEA) and lateral (LEA) entorhinal areas. MEA fields ECL and EC are characterised by a poor differentiation between layers II and III, a distinct layer IV and broad, stratified layers V and VI. LEA fields EI, ER and EL are distinguished by cell clusters in layer II, a clear differentiation between layers II and III, a wide columnar layer III, and a broad sublayer Va. Clustering in LEA layer II was more typical of the Straw-coloured fruit bat. Timm-staining was most intense in layers Ib and II across all fields, and layer III of field ER. Parvalbuminlike staining varied along a medio-lateral gradient with highest immunoreactivity in layers II and III of MEA and more lateral fields of LEA. Sparse SMI-32-like immunoreactivity was seen only in Wahlberg’s epauletted fruit bat. Of the neurons in MEA layer II, ovoid stellate cells account for ~38%, polygonal stellate cells for ~8%, pyramidal cells for ~18%, oblique pyramidal cells for ~6%, and other neurons of variable morphology for ~29%. Differences between bats and other species in cellular make-up and cytoarchitecture of layer II may relate to their 3-dimensional habitat. Cytoarchitecture of layer V in conjunction with high encephalisation and structural changes in the hippocampus suggest similarities in efferent hippocampal-entorhinal-cortical interactions between fruit bats and primates