The neural response to amplitude-modulated sinus sounds (AM sound) was investigated in the auditory cortex and insula of the awake squirrel monkey. It was found that 78.1% of all acoustically driven neurons encoded the envelope of the AM sound; the remaining 21.9% displayed simple On, On/Off or Off responses at the beginning or the end of the stimulus sound. Those neurons with AM coding were able to encode the AM sound frequency in two different ways: (1) the spikes followed the amplitude modulation envelopes in a phase locked manner; (2) the spike rate changed significantly with changing modulation frequencies. As reported in other species, the modulation transfer functions for rate showed higher modulation frequencies than the phase-locked response. Both AM codings exhibited a filter characteristic for AM sound. Whereas 46.6% of all neurons had the same filter characteristic for both the spike discharge and the phase-locked response, the remaining neurons displayed combinations of different filter types. The discharge pattern of a neuron to simple tone or noise bursts suggests the behaviour of this neuron when AM sound is used as the stimulus. Neurons with strong onset responses to tone/noise bursts tended to have higher phase-locked AM responses than neurons with weak onset responses. The spike rate maxima for AM sound showed no relation to the tone/noise burst discharge patterns. Varying modulation depth was encoded by the neuron's ability to follow the envelope cycles and not by the non-phase-locked spike rate frequency. The organization of the squirrel monkey's auditory cortex has previously been established by an anatomical study. We have added two new fields using physiological parameters. All fields investigated showed a clear functional separation for time-critical information processing. The best temporal resolution was shown by the primary auditory field (AI), the first-temporal field (T1) and the parainsular auditory field (Pi). The neural data in these fields and the amplitude modulation frequency range of squirrel monkey calls suggest a similar correlation between vocalization and perception as in human psychophysical data for speech and hearing sensation. The anterior fields in particular failed to follow the AM envelopes. For the first time in a primate, the insula was tested with different sound parameters ranging from simple tone bursts to AM sound. It is suggested that this cortical region plays a role in time-critical aspects of acoustic information processing. The observed best frequencies covered the same spectrum as AI. As in the auditory fields, most neurons in the insula encoded AM sound with different filter types. The high proportion of neurons unable to encode AM sound (40.6%) and the low mean best modulation frequency (9.9 Hz) do not support a prominent role of the insula in temporal information processing.

In this study the effect of immune system stimulation and intracerebroventricular (i.c.v.) administration of interleukin-1 beta (IL-1 beta) on hippocampal serotonergic neurotransmission, behavioral activity, and the hypothalamic-pituitary-adrenocortical (HPA) axis is described. An in vivo microdialysis method was used to measure hippocampal extracellular concentrations of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in conscious, freely moving rats. In addition, we established a method to continuously monitor free corticosterone levels in dialysates. Behavioral activity was scored by measuring the time during which rats were active (locomotion, grooming, eating, drinking). We found a significant, positive relationship between behavioral activity and hippocampal extracellular concentrations of 5-HT. Intraperitoneal (i.p.) administration of the bacterial endotoxin lipopolysaccharide (LPS; 30, 100, and 300 micrograms/kg body weight) produced an increase in the extracellular concentrations of 5-HT and 5-HIAA in the hippocampus, which was paralleled by a significant decline in behavioral activity and a marked increase in extracellular corticosterone levels. Thus, the close correlation between hippocampal extracellular 5-HT levels and behavioral activity observed in control rats was disrupted in the LPS-treated animals. The effects of i.p. LPS could be mimicked by i.c.v. application of recombinant human IL-1 beta (hIL-1 beta; 100 ng). i.c.v. pretreatment with the IL-1 receptor antagonist (IL-1ra; 10 micrograms) antagonized the hIL-1 beta-induced effects. IL-1ra showed no intrinsic effects. Furthermore, it was found that i.c.v. pretreatment with IL-1ra (10 micrograms) significantly attenuated the i.p. LPS-induced (100 micrograms/kg body weight) rise in hippocampal extracellular 5-HT levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired sleep and enhanced stress hormone secretion are the hallmarks of stress-related disorders, including major depression. The central neuropeptide, corticotropin-releasing hormone (CRH), is a key hormone that regulates humoral and behavioral adaptation to stress. Its prolonged hypersecretion is believed to play a key role in the development and course of depressive symptoms, and is associated with sleep impairment. To investigate the specific effects of central CRH overexpression on sleep, we used conditional mouse mutants that overexpress CRH in the entire central nervous system (CRH-COE-Nes) or only in the forebrain, including limbic structures (CRH-COE-Cam). Compared with wild-type or control mice during baseline, both homozygous CRH-COE-Nes and -Cam mice showed constantly increased rapid eye movement (REM) sleep, whereas slightly suppressed non-REM sleep was detected only in CRH-COE-Nes mice during the light period. In response to 6-h sleep deprivation, elevated levels of REM sleep also became evident in heterozygous CRH-COE-Nes and -Cam mice during recovery, which was reversed by treatment with a CRH receptor type 1 (CRHR1) antagonist in heterozygous and homozygous CRH-COE-Nes mice. The peripheral stress hormone levels were not elevated at baseline, and even after sleep deprivation they were indistinguishable across genotypes. As the stress axis was not altered, sleep changes, in particular enhanced REM sleep, occurring in these models are most likely induced by the forebrain CRH through the activation of CRHR1. CRH hypersecretion in the forebrain seems to drive REM sleep, supporting the notion that enhanced REM sleep may serve as biomarker for clinical conditions associated with enhanced CRH secretion.

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