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We have previously established that PV+ neurons and Npas1+ neurons are distinct neuron classes in the external globus pallidus (GPe): they have different topographical, electrophysiological, circuit, and functional properties. Aside from Foxp2+ neurons, which are a unique subclass within the Npas1+ class, we lack driver lines that effectively capture other GPe neuron subclasses. In this study, we examined the utility of Kcng4-Cre, Npr3-Cre, and Npy2r-Cre mouse lines (both males and females) for the delineation of GPe neuron subtypes. By using these novel driver lines, we have provided the most exhaustive investigation of electrophysiological studies of GPe neuron subtypes to date. Corroborating our prior studies, GPe neurons can be divided into two statistically distinct clusters that map onto PV+ and Npas1+ classes. By combining optogenetics and machine learning-based tracking, we showed that optogenetic perturbation of GPe neuron subtypes generated unique behavioral structures. Our findings further highlighted the dissociable roles of GPe neurons in regulating movement and anxiety-like behavior. We concluded that Npr3+ neurons and Kcng4+ neurons are distinct subclasses of Npas1+ neurons and PV+ neurons, respectively. Finally, by examining local collateral connectivity, we inferred the circuit mechanisms involved in the motor patterns observed with optogenetic perturbations. In summary, by identifying mouse lines that allow for manipulations of GPe neuron subtypes, we created new opportunities for interrogations of cellular and circuit substrates that can be important for motor function and dysfunction. [ABSTRACT FROM AUTHOR]

Ambient GABA in the brain tonically activates extrasynaptic GABAA receptors, and activity-dependent changes in ambient GABA concentration can also activate GABAB receptors. To investigate an interaction between postsynaptic GABAB and GABAA receptors, we recorded GABAA currents elicited by exogenous GABA (10μm) from dentate gyrus granule cells (DGGCs) in adult rat hippocampal slices. The GABAB receptor agonist baclofen (20μm) enhanced GABAA currents. This enhancement was blocked by the GABAB receptor antagonist CGP 55845 and intracellular solutions containing the GTP analog GDP-β-s, indicating that baclofen was acting on postsyn-aptic GABAg receptors. Modulation of GABAA currents by postsynaptic GABABreceptors was not observed in CA1 pyramidal cells or layer 2/3 cortical pyramidal neurons. Baclofen reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) but did not alter sIPSC amplitude or kinetics. Thus, GABAA receptors activated at synapses were not modulated by postsynaptic GABAB recep-tors. In contrast, tonic GABA currents and currents activated by the GABAA receptor δ subunit-selective agonist THIP (10μM) were potentiated by baclofen. Our data indicate that postsynaptic GABAB receptors enhance the function of extrasynaptic GABAa receptors, including 8 subunit-containing receptors that mediate tonic inhibition in DGGCs. The modulation of GABAA receptor function by postsynaptic GABAB receptors is a newly identified mechanism that will influence the inhibitory tone of DGGCs when GABAB and GABAA receptors are both activated. [ABSTRACT FROM AUTHOR]

While adaptation is widely thought to facilitate neural coding, the form of adaptation should depend on how the signals are encoded. Monaural neurons early in the interaural time difference (ITD) pathway encode the phase of sound input using spike timing rather than firing rate. Such neurons in chicken nucleus magnocellularis (NM) adapt to ongoing stimuli by increasing firing rate and decreasing spike timing precision. We measured NM neuron responses while adapting them to simulated physiological input, and used these responses to construct inputs to binaural coincidence detector neurons in nucleus laminaris (NL). Adaptation of spike timing in NM reduced ITD sensitivity in NL, demonstrating the dominant role of timing in the short-term plasticity as well as the immediate response of this sound localization circuit. [ABSTRACT FROM AUTHOR]

The frequency response properties of neurons are critical for signal transmission and control of network oscillations. At subthreshold membrane potential, some neurons show resonance caused by voltage-gated channels. During action potential firing, resonance of the spike output may arise from subthreshold mechanisms and/or spike-dependent currents that cause afterhyperpolarizations (AHPs) and afterdepolarizations (ADPs). Layer 2-3 pyramidal neurons (L2-3 PNs) have a fast ADP that can trigger bursts. The present study investigated what stimuli elicit bursting in these cells and whether bursts transmit specific frequency components of the synaptic input, leading to resonance at particular frequencies. We found that two-spike bursts are triggered by step onsets, sine waves in two frequency bands, and noise. Using noise adjusted to elicit firing at ~10 Hz, we measured the gain for modulation of the time-varying firing rate as a function of stimulus frequency, finding a primary peak (7-16 Hz) and a high-frequency resonance (250-450 Hz). Gain was also measured separately for single and burst spikes. For a given spike rate, bursts provided higher gain at the primary peak and lower gain at intermediate frequencies, sharpening the high-frequency resonance. Suppression of bursting using automated current feedback weakened the primary and high-frequency resonances. The primary resonance was also influenced by the SK channel-mediated medium AHP (mAHP), because the SK blocker apamin reduced the sharpness of the primary peak. Our results suggest that resonance in L2-3 PNs depends on burst firing and the mAHP. Bursting enhances resonance in two distinct frequency bands. [ABSTRACT FROM AUTHOR]

Adaptation is commonly defined as a decrease in response to a constant stimulus. In the auditory system such adaptation is seen at multiple levels. However, the first-order central neurons of the interaural time difference detection circuit encode information in the timing of spikes rather than the overall firing rate. We investigated adaptation during in vitro whole-cell recordings from chick nucleus magnocellularis neurons. Injection of noisy, depolarizing current caused an increase in firing rate and a decrease in spike time precision that developed over ~20 s. This adaptation depends on sustained depolarization, is independent of firing, and is eliminated by α-dendrotoxin (0.1 μM), implicating slow inactivation of low-threshold voltage-activated K+ channels as its mechanism. This process may alter both firing rate and spike-timing precision of phase-locked inputs to coincidence detector neurons in nucleus laminaris and thereby adjust the precision of sound localization. [ABSTRACT FROM AUTHOR]

Neuronal firing is known to depend on the variance of synaptic input as well as the mean input current. Several studies suggest that input variance, or "noise," has a divisive effect, reducing the slope or gain of the firing frequency--current (f--I) relationship. We measured the effects of current noise on f--I relationships in pyramidal neurons and fast-spiking (FS) interneurons in slices of rat sensorimotor cortex. In most pyramidal neurons, noise had a multiplicative effect on the steady-state f--I relationship, increasing gain. In contrast, noise reduced gain in FS interneurons. Gain enhancement in pyramidal neurons increased with stimulus duration and was correlated with the amplitude of the slow afterhyperpolarization (sAHP), a major mechanism of spike-frequency adaptation. The 5-HT2 receptor agonist α-methyl-5-HT reduced the sAHP and eliminated gain increases, whereas augmenting the sAHP conductance by spike-triggered dynamic-current clamp enhanced the gain increase. These results indicate that the effects of noise differ fundamentally between classes of neocortical neurons, depending on specific biophysical properties including the sAHP conductance. Thus, noise from background synaptic input may enhance network excitability by increasing gain in pyramidal neurons with large sAHPs and reducing gain in inhibitory FS interneurons. [ABSTRACT FROM AUTHOR]