No abstract

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts’ assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus.

A key feature of the mammalian brain is its capacity to adapt in response to experience, in part by remodeling of synaptic connections between neurons. Excitatory synapse rearrangements have been monitored in vivo by observation of dendritic spine dynamics, but lack of a vital marker for inhibitory synapses has precluded their observation. Here, we simultaneously monitor in vivo inhibitory synapse and dendritic spine dynamics across the entire dendritic arbor of pyramidal neurons in the adult mammalian cortex using large volume high-resolution dual color two-photon microscopy. We find that inhibitory synapses on dendritic shafts and spines differ in their distribution across the arbor and in their remodeling kinetics during normal and altered sensory experience. Further, we find inhibitory synapse and dendritic spine remodeling to be spatially clustered, and that clustering is influenced by sensory input. Our findings provide in vivo evidence for local coordination of inhibitory and excitatory synaptic rearrangements.

No abstract

1. To test the hypothesis that physiologically and morphologically different cortical nonpyramidal cells express different calcium-binding proteins, whole-cell current-clamp recording in vitro was combined with intracellular staining and double immunofluorescence in layer V of frontal cortex of rats 16-20 days old. 2. Nonpyramidal cells were first characterized as fast-spiking (FS) or low-threshold spike (LTS) cells, injected with biocytin, and subsequently stained immunohistochemically for parvalbumin and calbindinD28k. 3. FS cells were identified by input resistances < 350 M omega, spike width at half amplitude < 0.8 ms, and virtually no spike frequency adaptation of spike trains by depolarizing pulses. LTS cells were identified by input resistances > 350 M omega, spike width at half amplitude > 0.8 ms, and the discharge of low-threshold spikes from hyperpolarized potentials. Repetitive firing could be induced by a combination of stimulation-induced excitatory postsynaptic potentials with depolarization in FS cells. Repetitive firing was not observed in LTS cells under these conditions. 4. After biocytin injection of layer V cells characterized in this way, subsequent double immunostaining showed that all biocytin-labeled parvalbumin-immunoreactive cells (n = 18) belonged to the FS cells (FS-PV cells), whereas all biocytin-labeled calbindinD28k-immunoreactive cells (n = 10) belonged to the LTS cells (LTS-Calb cells). 5. FS-PV cells had smooth or sparsely spiny dendrites, whereas LTS-Calb cells had dendrites with a modest number of spines but fewer than pyramidal cells. FS-PV cells showed denser axonal branches near their somata and extended axons in a more horizontal direction. Some of them could be identified as basket cells by the presence of terminal boutons surrounding somata of other cells. LTS-Calb cells extended their main axons more vertically up to layer I. 6. Double immunofluorescent staining revealed that very few cells in layer V showed immunoreactivity for both calcium-binding proteins but that most cells immunoreactive for the calcium-binding proteins in layer V were also immunoreactive for gamma-aminobutyric acid. 7. These results suggest that GABAergic nonpyramidal cells in layer V of neocortex can be divided into two functional groups on the basis of different firing modes, axonal distributions, and calcium-binding protein immunoreactivity: 1) FS-PV cells show repetitive firing by synaptic activation, have axonal arborizations that are more dense near their somata and oriented horizontally, and the cells exhibit parvalbumin immunoreactivity and 2) LTS cells show low-threshold spikes, have more vertical axonal arborizations up to layer I, and exhibit calbindinD28K immunoreactivity.

Physiological and morphological characteristics of GABAergic nonpyramidal cells in frontal cortex of young rats identified immunohistochemically as containing somatostatin or vasoactive intestinal polypeptide (VIP) were studied in vitro by whole-cell recording and biocytin injection. We have found that most somatostatin- or VIP-containing neurons were different from two other types of GABAergic cells, the parvalbumin-containing fast-spiking cells and the late-spiking cells (neurogliaform cells). In response to injected currents, somatostatin- or VIP-containing nonpyramidal cells showed either bursts of a few spikes on a slow-depolarizing hump, burst-spiking nonpyramidal cells, or single spikes only on depolarization, regular-spiking nonpyramidal cells. Morphologically, both somatostatin- and VIP-containing cells had vertical axonal arbors terminating in symmetrical synapses that were immunoreactive for GABA in electron micrographs. Somatostatin cells included neurons with main ascending axons sending collaterals into layer I (Martinotti cells in deep layers). Some of the Martinotti cells in layer V also contained calbindin D 28k. VIP cells included neurons the main descending axons of which had more descending than ascending collaterals (bipolar cells and double bouquet cells). Two other morphological forms of the VIP cells were those with short descending axons with collaterals bearing multiple boutons on other cell bodies (small basket cells) or with short ascending main axons with collaterals forming arcades (arcade cells). Some of these neurons also contained calretinin. From these results, it appears that the GABAergic neurons controlling circuits in the neocortical layers may be characterized further based on whether they contain somatostatin or VIP.

No abstract

While inhibition has been implicated in mediating plasticity in the adult brain, the mechanism remains unclear. Here we present a structural mechanism for the role of inhibition in experience-dependent plasticity. Using chronic in vivo two-photon microscopy in the mouse neocortex we show that experience drives structural remodeling of superficial layer 2/3 interneurons in an input- and circuit-specific manner, with up to 16% of branch tips remodeling. Visual deprivation initially induces dendritic branch retractions accompanied by loss of inhibitory inputs onto neighboring pyramidal cells. The resulting decrease in inhibitory tone, also achievable pharmacologically by the antidepressant fluoxetine, provides a permissive environment for further structural adaptation, including addition of new synapse bearing branch tips. Our findings suggest that therapeutic approaches that reduce inhibition, when combined with an instructive stimulus, could facilitate restructuring of mature circuits impaired by damage or disease, improving function and perhaps enhancing cognitive abilities.