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Spontaneous firing and behavior-related changes in discharge profiles of basal forebrain (BF) neurons are well documented, albeit the mechanisms underlying the variety of activity modes and intermodal transitions remain elusive. With the use of cell-attached recordings, this study identifies a range of spiking patterns in diagonal band Broca (DBB) noncholinergic cells of rats and tentatively categorizes them into low-rate random, tonic, and cluster firing activities. It demonstrates further that the multiplicity of discharge profiles is sustained intrinsically and persists after blockade of glutamate-, glycine/GABA-, and cholinergic synaptic inputs. Stimulation of muscarinic receptors, blockade of voltage-gated Ca(2+)-, and small conductance (SK) Ca(2+)-activated K(+) currents as well as chelating of intracellular Ca(2+) concentration accelerate low-rate random and tonic firing and favor transition of neurons into cluster firing mode. A similar trend towards higher discharge rates with switch of neurons into cluster firing has been revealed by activation of neuropeptide Y (NPY) receptors with the NPY or NPY(1) receptor agonist [Leu(31),Pro(34)]-NPY. Whole cell current-clamp analysis demonstrates that the variety of spiking modes and intermodal transitions could be induced within the same neuronal population by injection of bias depolarizing or hyperpolarizing currents. Taken together, these data demonstrate the intrinsic and highly variable character of regenerative firing in BF noncholinergic cells, subject to powerful modulation by classical neurotransmitters, NPY, and small membrane currents.

The leaner mouse mutation of the Cacna1a gene leads to a reduction in P-type Ca2+ current, the dominant Ca2+ current in Purkinje cells (PCs). Here, we compare the electro-responsiveness and structure of PCs from age-matched leaner and wild-type (WT) mice in pharmacological isolation from synaptic inputs in cerebellar slices. We report that compared with WT, leaner PCs exhibit lower current threshold for Na+ spike firing, larger subthreshold membrane depolarization, rapid adaptation followed by complete block of Na+ spikes upon strong depolarization, and fail to generate Ca2+-Na+ spike bursts. The Na+ spike waveforms in leaner PCs have slower kinetics, reduced spike amplitude and afterhyperpolarization. We show that a deficit in the P-type Ca2+ current caused by the leaner mutation accounts for most but not all of the changes in mutant PC electro-responsiveness. The selective P-type Ca2+ channel blocker, omega-agatoxin-IVA, eliminated differences in subthreshold membrane depolarization, adaptation of Na+ spikes upon strong current-pulse stimuli, Na+ spike waveforms and Ca2+-Na+ burst activity. In contrast, a lower current threshold for eliciting repetitive Na+ spikes in leaner PCs was still observed after blockade of the P-type Ca2+ current, suggesting secondary effects of the mutation that render PCs hyper-excitable. Higher input resistance, reduced whole-cell capacitance and smaller dendritic size accompanied the enhanced excitability in leaner PCs, indicative of developmental retardation in these cells caused by P/Q-type Ca2+ channel malfunction. Our data indicate that a deficit in P-type Ca2+ current leads to complex functional and structural changes in PCs, impairing their intrinsic and integrative properties.

Frog spinal neurons receive a prominent innervation from the bulbar serotonergic nuclear complex. We used an isolated spinal cord preparation to examine the effect of serotonin (5-hydroxytryptamine, 5-HT) receptor activation on segmental and descending monosynaptic excitatory inputs to frog lumbar motoneurons. Bath-application of 5-HT (0.05 mM) caused a significant reduction in the peak amplitude of segmental EPSP elicited by dorsal root (DR) stimulation (P < 0.05). Contrasting to DR evoked responses 5-HT did not affect the descending monosynaptic EPSP conditioned by ventrolateral column (VLC) stimulation. Recording of the VLC induced EPSP-spike (E-S) field response within the ventral horn motor nucleus disclosed a substantial enhancement in the population discharge of motoneurons upon 5-HT application (P < 0.05). These data suggest the potential importance of serotonergic receptors in motor integration and gaining of motor output in the frog spinal cord.

The effects of GABA, bicuculline and 5-HT on primary afferents in the isolated spinal cord of the frog Rana ridibunda were studied. Bath application of GABA (1 mM) reduced the primary afferent depolarisation (PAD) in IX segment of the spinal cord evoked by X dorsal root stimulation (57 +/- 8% of initial level, n = 5, p < 0.05). The action potentials (AP) recorded in dorsal root afferents was also suppressed under the GABA action (74 +/- 9%, p < 0.05). Bath application of bicuculline (50 microM) reduced the PAD (21 +/- 7%), n = 6, p < 0.05), meanwhile the AP in dorsal root afferents was resistant against the bicuculline action. Bath application of 5-HT (25 microM) depressed the PAD (34 +/- 7%, n = 7, p < 0.05) and the amplitude of the AP recorded from the single afferent fibre in dorsal column (76 +/- 6%, n = 7, p < 0.05). In contrast to GABA, 5-HT more effectively suppressed the late phase of the PAD evoked by X dorsal root stimulation and caused (76 +/- 6%, n = 7, p < 0.05) an alteration of the AP shape. All effects induced by these drugs were reversible. The mechanisms of GABA and 5-HT modulation of spinal cord afferent income are discussed.