Abstracts

The mechanisms controlling excitability in the neocortex are not well understood. The intrinsic and synaptic properties of low threshold-spiking (LTS) cells, a specific type of inhibitory interneuron, make them good candidates for regulating overall cortical activity. However, the circumstances under which LTS cells are activated, as well as the consequences of their activation, are unknown. We performed whole-cell patch clamp recordings from LTS, regular spiking (RS), and fast spiking (FS) cells in layer 2/3 of slices from rat somatosenosory cortex of GIN mice (Oliva et al. 2000), which express green fluorescent protein in somatostatin-expressing interneurons (including LTS cells). We then evoked firing in LTS cells in several ways: 1) presentation of a brief tetanic stimulus (20 shocks at 100 Hz) to upper layer 4; 2) application of artificial cerebrospinal fluid (ACSF) containing high [K⁺] (6-10 mM); 3) application of ACSF containing low divalent ions ([Mg²⁺] and [Ca²⁺] both 1 mM). We demonstrated that persistent activity could be evoked in LTS neurons under 3 conditions. First, following a brief extracellular tetanic pulse to layer 4, LTS neurons hyperpolarized for several seconds, and then depolarized and fired for tens of seconds at a rate of 2-8 Hz. Antagonists of AMPA, NMDA and GABA[sub]A[/sub] receptors did not block this persistent firing, suggesting that it does not depend on fast synaptic transmission. Persistent firing was blocked, partially or entirely, by antagonists of mGluR1 receptors. Second, when ACSF containing either high [K⁺], or low-divalent cation concentrations was applied, LTS neurons depolarized and fired tonically at a rate of approximately 2-7 Hz. In addition, when low-divalent ACSF was applied, LTS neurons participated in up-states, which have previously been described under such conditions. In contrast to LTS neurons, fast-spiking (FS) interneurons and regular-spiking (RS) excitatory neurons did not respond to tetanic stimuli with persistent firing, and they did not fire tonically in high [K⁺] or low-divalent ACSF. These results demonstrate that LTS interneurons become persistently active in response to a number of manipulations that increase overall activity in the neocortical network, whereas FS interneurons and pyramidal neurons are not activated for long periods under these conditions. Such tonic firing in LTS interneurons could serve to control the general excitability of the local cortical circuit. (Supported by the Epilepsy Foundation through the generous support of the American Epilepsy Society and the Milken Family Foundation, and by NS25983 and NS050434.)