Networks In Neocortex Research Articles

Taurine activates GABAergic networks in the neocortex of immature mice

Although it has been suggested that taurine is the main endogenous neurotransmitter acting on glycine receptors, the implications of glycine receptor-mediated taurine actions on immature neocortical networks have not been addressed yet. To investigate the influence of taurine on the excitability of neuronal networks in the immature neocortex, we performed whole-cell patch-clamp recordings from visually identified pyramidal neurons and interneurons in coronal slices from C57Bl/6 and GAD67-green fluorescent protein (GFP) transgenic mice (postnatal days 2–4). In 46% of the pyramidal neurons bath-application of taurine at concentrations ≥ 300 μM significantly enhanced the frequency of postsynaptic currents (PSCs) by 744.3 ± 93.8% (n = 120 cells). This taurine-induced increase of PSC frequency was abolished by 0.2 μM tetrodotoxin (TTX), 1 μM strychnine or 3 μM gabazine, but was unaffected by the glutamatergic antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and (±) R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP), suggesting that taurine specifically activates GABAergic network activity projecting to pyramidal neurons. Cell-attached recordings revealed that taurine enhanced the frequency of action potentials (APs) in pyramidal neurons, indicating an excitatory action of the GABAergic PSCs. In order to identify the presynaptic targets of taurine we demonstrate that bath application of taurine induced in GAD67-GFP labeled interneurons an inward current that is mainly mediated by glycine receptors and can generate APs in these cells. We conclude from these results that taurine can enhance network excitability in the immature neocortex by selectively activating GABAergic interneurons via interactions with glycine receptors.

Plasticity of Recurrent L2/3 Inhibition and Gamma Oscillations by Whisker Experience

Local recurrent networks in neocortex are critical nodes for sensory processing, but their regulation by experience is much less understood than for long-distance (translaminar or cross-columnar) projections. We studied local L2/3 recurrent networks in rat somatosensory cortex during deprivation-induced whisker map plasticity, by expressing channelrhodopsin-2 (ChR2) in L2/3 pyramidal cells and measuring light-evoked synaptic currents in exvivo S1 slices. In columns with intact whiskers, brief light impulses evoked recurrent excitation and supralinear inhibition. Deprived columns showed modestly reduced excitation and profoundly reduced inhibition, providing a circuit locus for disinhibition of whisker-evoked responses observed in L2/3 invivo. Slower light ramps elicited sustained gamma frequency oscillations, which were nearly abolished in deprived columns. Reduction in gamma power was also observed in spontaneous LFP oscillations in L2/3 of deprived columns invivo. Thus, L2/3 recurrent networks are a powerful site for homeostatic modulation of excitation-inhibition balance and regulation of gamma oscillations.

Area‐Specific Resonance of Excitatory Networks in Neocortex: Control by Outward Currents

During disinhibition or low [Mg++](o) buffer, 7-14 Hz ( approximately 10 Hz) oscillations are generated by excitatory networks of interconnected pyramidal cells in motor (agranular) cortex but are absent in barrel (granular) cortex. Here we studied if the inability of barrel cortex to produce approximately 10 Hz oscillations during these conditions is because barrel cortex networks lack the necessary cellular mechanisms or, alternatively, because those mechanisms are inhibited by outward currents. The results show that blockers of slowly inactivating voltage-dependent K+ currents unmask approximately 10 Hz oscillations in barrel cortex, and this occurs in unison with the unmasking of intrinsic inward Ca++ currents that are kept suppressed by the outward currents. Moreover, the approximately 10 Hz oscillations unmasked in barrel cortex occur independently in upper and lower layers indicating that the approximately 10 Hz oscillation mechanisms are kept suppressed in multiple networks. The results reveal that the propensity of distinct excitatory networks of neocortex to generate epileptiform oscillatory activities is controlled by outward currents.

Global dendritic calcium spikes in mouse layer 5 low threshold spiking interneurones: implications for control of pyramidal cell bursting.

Interneuronal networks in neocortex underlie feedforward and feedback inhibition and control the temporal organization of pyramidal cell activity. We previously found that lower layer neocortical interneurones can reach action potential threshold in response to the stimulation of a single presynaptic cell. To better understand this phenomenon and the circuit roles of lower layer neocortical interneurones, we combined two-photon calcium imaging with whole cell recordings and anatomical reconstructions of low threshold spiking (LTS) interneurones from mouse neocortex. In both visual and somatosensory cortex, LTS interneurones are somatostatin-positive, concentrated in layer 5 and possess dense axonal innervation to layer 1. Due to the LTS properties, these neurones operate in burst and tonic modes. In burst mode, dendritic T-type calcium channels boosted small synaptic inputs and triggered low threshold calcium spikes, while in tonic mode, sodium-based APs evoked smaller calcium influxes. In both modes, the entire dendritic tree of LTS interneurones behaved as a 'global' single spiking unit. This, together with the fact that synaptic inputs to layer 5 LTS cells are facilitating, and that their axons target the dendritic region of the pyramidal neurones where bursts are generated, make these neurones ideally suited to detect and control burst generation of individual lower layer pyramidal neurones.