04.2013 - TEM study on VIP interneurons in barrel cortex group led by Prof. Staiger J.F.
06.2012 Get DAAD Ph.D. scholarship
09.2009‐06.2012 M.Sc. in Basic Psychology, School of Cognitive Psychology, East China Normal University, Shanghai, China
09.2005-06.2009 B.A. in Animal Science, School of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Interneurons in neocortex can be divided into three distinct groups by their expressed molecular, PV+ interneuron, SOM+ interneuron, and VIP+ interneuron (Xu et al., 2010). Among the three groups, VIP+ interneurons seem to be the lowest in population and have been least studied by researchers. Most VIP interneurons VIP neurons in hippocampus are interneuron-specific interneurons, i.e. exlcusively controlling (orchestrating) other GABAergic interneurons. For the cortex this is assumed as well but was never really proven. Evidence shows that VIP interneurons could target other interneurons in specific layers but with the same axons of pyramidal cells in other layers. Due to their two opposite kinds of targeting, VIP interneurons may not be a typical inhibitory interneuron.
To explore the problem, we want to detect the possible targets of VIP interneurons by using transmission electron microscopy techniques. We do experiments on the transgenic mice (VIP Cre-dtomato) whose florescence signals can only be detected in VIP interneurons. We cooperate with Alvar Prönneke, the Ph.D. students who do electrophysiological study on VIP interneurons, fill them with biocytin, and reconstruct them under Neurolucida. Our goal is to explore the connectivity of VIP interneurons in order to help understand their functions in sematosensory cortex.
Somatostatin‐expressing (SST+) cells form the second largest subpopulation of neocortical GABAergic neurons that contain diverse subtypes, which participate in layer‐specific cortical circuits. Martinotti cells, as the most abundant subtype of SST+ interneurons, are mainly located in layers II/III and V/VI, and are characterized by dense axonal arborizations in layer I. GFP‐expressing inhibitory neurons (GIN), representing a fraction of mainly upper layer SST+ interneurons in various cortical areas, were recently claimed to include both Martinotti cells and non‐Martinotti cells. This makes it necessary to examine in detail the morphology and synaptic innervation pattern of the GIN cells, in order to better predict their functional implications. In our study, we characterized the neurochemical specificity, somatodendritic morphology, synaptic ultrastructure as well as synaptic innervation pattern of GIN cells in the barrel cortex in a layer‐specific manner. We showed that GIN cells account for 44% of the SST+ interneurons in layer II/III and around 35% in layers IV and Va. There are 29% of GIN cells coexpressing calretinin with 54% in layer II/III, 8% in layer IV, and 13% in layer V. They have diverse somatodendritic configurations and form relatively small synapses across all examined layers. They almost exclusively innervate dendrites of excitatory cells, preferentially targeting distal apical dendrites and apical dendritic tufts of pyramidal neurons in layer I, and rarely target other inhibitory neurons. In summary, our study reveals unique features in terms of the morphology and output of GIN cells, which can help to better understand their diversity and structure–function relationships.
Neocortical vasoactive intestinal polypeptide (VIP) expressing cells are a diverse subpopulation of GABAergic interneurons issuing distinct axonal projections. They are known to inhibit other types of interneurons as well as excitatory principal neurons and possess a disinhibitory net effect in cortical circuits. In order to elucidate their targeting specificity, the output connectivity of VIP interneurons was studied at the subcellular level in barrel cortex of interneuron-specific Cre-driver mice, using pre- and postembedding electron microscopy. Systematically sampling VIP boutons across all layers, we found a substantial proportion of the innervated subcellular structures were dendrites (80%), with somata (13%), and spines (7%) being much less targeted. In layer VI, a high proportion of axosomatic synapses was found (39%). GABA-immunopositive ratio was quantified among the targets using statistically validated thresholds: only 37% of the dendrites, 7% of the spines, and 26% of the somata showed above-threshold immunogold labeling. For the main target structure "dendrite", a higher proportion of GABAergic subcellular profiles existed in deep than in superficial layers. In conclusion, VIP interneurons innervate non-GABAergic excitatory neurons and interneurons at their subcellular domains with layer-dependent specificity. This suggests a diverse output of VIP interneurons, which predicts multiple functionality in cortical circuitry beyond disinhibition