Impaired fast-spiking, suppressed cortical inhibition and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins

Voltage-gated K+ channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to −10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 −/− mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.

K(+) channel expression distinguishes subpopulations of parvalbumin- and somatostatin-containing neocortical interneurons

Kv3.1 and Kv3.2 K+ channel proteins form similar voltage-gated K+ channels with unusual properties, including fast activation at voltages positive to −10 mV and very fast deactivation rates. These properties are thought to facilitate sustained high-frequency firing. Kv3.1 subunits are specifically found in fast-spiking, parvalbumin (PV)-containing cortical interneurons, and recent studies have provided support for a crucial role in the generation of the fast-spiking phenotype. Kv3.2 mRNAs are also found in a small subset of neocortical neurons, although the distribution of these neurons is different. We raised antibodies directed against Kv3.2 proteins and used dual-labeling methods to identify the neocortical neurons expressing Kv3.2 proteins and to determine their subcellular localization. Kv3.2 proteins are prominently expressed in patches in somatic and proximal dendritic membrane as well as in axons and presynaptic terminals of GABAergic interneurons. Kv3.2 subunits are found in all PV-containing neurons in deep cortical layers where they probably form heteromultimeric channels with Kv3.1 subunits. In contrast, in superficial layer PV-positive neurons Kv3.2 immunoreactivity is low, but Kv3.1 is still prominently expressed. Because Kv3.1 and Kv3.2 channels are differentially modulated by protein kinases, these results raise the possibility that the fast-spiking properties of superficial- and deep-layer PV neurons are differentially regulated by neuromodulators. Interestingly, Kv3.2 but not Kv3.1 proteins are also prominent in a subset of seemingly non-fast-spiking, somatostatin- and calbindin-containing interneurons, suggesting that the Kv3.1–Kv3.2 current type can have functions other than facilitating high-frequency firing.

Tractament lexicogràfic dels adjectius: aspectes a considerar

La informació gramatical més habitual de les entrades en un diccionari es basa quasi exclusivament en consignar la categoria sintàctica dels mots. Aquest plantejament suposa una parcel·lació massa vaga de les unitats lingüístiques, atès que en l'ús i la combinació entre elles hi entren en joc altres característiques, les quals porten a subclassificacions més precises a l'interior de les categories gramaticals. Un plantejament lexicogràfic que presenti un tractament detallat de les categories quant a les seves subclasses possibles és, a més d'útil en l'elaboració de diccionaris per a parlants de llengua estrangera, necessari també en diccionaris per a parlants natius de la llengua si, tal com és de suposar, l'ús que s'espera d'un diccionari va més enllà de la simple consulta del significat dels mots.En aquest article s'analitzen alguns dels punts que cal que els diccionaris tinguin en compte per a la descripció de l'ús real dels adjectius, es revisa quin és el tractament que reben en el diccionari pres com a font de referència (Diccionari de la Llengua Catalana (1994), d'Enciclopèdia Catalana) i s'esbossa una proposta de tractament per poder donar compte d'aquests aspectes. L'interès recau tant en qüestions d'ordre superficial dels constituents (la posició típica de les unitats), com aspectes sintàctics (la capacitat predicativa dels elements, la subcategorització de complements), així com també aspectes de tipus semàntic (la relació entre les denotacions de l'adjectiu i el substantiu, la facultat de graduabilitat dels adjectius).