[The auditory system in sleep]. / El sistema auditivo en el ciclo sueño-vigilia.

INTRODUCTION: The sensory information that the central nervous system receives represents an enormous amount of data coming from the outer world and from the body itself. This constitutes a set of influences that affects the general brain developing as well as on the sleep-waking organization. DEVELOPMENT: We have proposed changes in the auditory information processing throughout the sleep-wakefulness cycle may be at least partially evidenced by single neurons extracellular recordings. We introduce the concept that the neural network organization during sleep vs that of wakefulness is different and can be modulated by sensory signals, and vice versa, the sensory input may be influenced by the central nervous system asleep or awake. During sleep the evoked firing of auditory units increases, decreases or remains similar to that observed during quiet wakefulness. There has been no auditory unit yet that stopped firing as the guinea pig enters sleep. Approximately half of the cortical neurons studied did not change firing rate when passing into sleep while others increased or decreased. Thus, the system is continuously aware of the environment. CONCLUSIONS: We postulate that those neurons that changed their evoked firing during sleep, increasing or decreasing, are part of active sleep processes. Thus, the continuous sensory information input to the brain during sleep may serve to 'sculpt', modulate, the brain by activity-dependent mechanisms of neural development as has been postulated for wakefulness.

[Sensory processing could be temporally organized by ultradian brain rhythms]. / El procesamiento sensorial podría estar organizado en el tiempo por ritmos cerebrales ultradianos.

INTRODUCTION: Neuronal activity of sensory systems depends on input from the environment, the body and the brain itself. Various rhythms have been shown to affect sensory processing, such as the waking-sleep cycle and hippocampal theta waves, our aim in this revision. The hippocampus, known as a structure involved in learning and memory processing, has the theta rhythm (4-10 Hz), present in all behavioural states. This rhythm has been temporally related to automatic, reflex and voluntary movements, both during wakefulness and sleep, and in the autonomic control of the heart rate. On the other hand theta rhythm has been considered as a novelty detector expressing different level of attention, selecting the information and protecting from interference. DEVELOPMENT AND CONCLUSIONS: Our research is based on the hypothesis that sensory processing needs a timer to be processed and stored, and hippocampal theta rhythm could contribute to the temporal organization of these events. We have demonstrated that auditory and visual unitary discharges in guinea pigs show phase-locking to the hippocampal theta rhythm. This temporal correlation appears during both spontaneous and specific sensory stimulation evoked discharges. Neuronal discharges fluctuate between phase-locked and uncorrelated firing modes relative to the theta rhythm. This changing state depends on known and unknown situations. We have provoked, changing the visual stimuli, a power theta rhythm increment and the phase-locking between this rhythm and the lateral geniculate neurone discharge during wakefulness. In slow wave sleep results were different demonstrating that the ways of the inputs processing have changed.

Auditory deprivation modifies biological rhythms in the golden hamster.

To assess to what extent auditory sensory deprivation affects biological rhythmicity, sleep/wakefulness cycle and 24 h rhythm in locomotor activity were examined in golden hamsters after bilateral cochlear lesion. An increase in total sleep time as well as a decrease in wakefulness (W) were associated to an augmented number of W episodes, as well as of slow wave sleep (SWS) and paradoxical sleep (PS) episodes in deaf hamsters. The number of episodes of the three behavioural states and the percent duration of W and SWS increased significantly during the light phase of daily photoperiod only. Lower amplitudes of locomotor activity rhythm and a different phase angle as far as light off were found in deaf hamsters kept either under light-dark photoperiod or in constant darkness. Period of locomotor activity remained unchanged after cochlear lesions. The results indicate that auditory deprivation disturbs photic synchronization of rhythms with little effect on the clock timing mechanism itself.

Reciprocal actions between sensory signals and sleep.

To the best of our knowledge, there is no simple way to induce neural networks to shift from waking mode into sleeping mode. Our best guess is that a whole group of neurons would be involved and that the process would develop in a period of time and a sequence which are mostly unknown. The quasi-total sensory deprivation elicits a new behavioral state called somnolence. Auditory stimulation as well as total auditory deprivation alter sleep architecture. Auditory units exhibiting firing shifts on passing to sleep (augmenting or diminishing) are postulated to be locked to sleep-related networks. Those ( approximately 50%) that did not change during sleep are postulated to continue informing the brain as in wakefulness. A rhythmic functional plasticity of involved networks is postulated. A number of auditory and visual cells have demonstrated a firing phase locking to the hippocampal theta rhythm. This phase locking occurs both during wakefulness and sleep phases. The theta rhythm may act as an organizer of sensory information in visual and auditory systems, in all behavioral states adding a temporal dimension to the sensory processing. Sensory information from the environment and body continuously modulates the central nervous system activity, over which sleep phenomenology must develop. It also produces a basal tonus during wakefulness and sleep, determining changes in the networks that contribute to sleep development and maintenance and, eventually, it also leads to sleep interruption.

Hippocampal theta waves as an electrocardiogram rhythm timer in paradoxical sleep.

Episodes of heart arrhythmia are present during paradoxical sleep, a known non-homeostatic--'open loop'--physiological state, while wakefulness and slow wave sleep exhibit 'closed-loop' control. A brain-stem autonomic oscillator, a hypothalamic and a corticofrontal center, entrained by baroreceptor input, has been proposed as the main heart rhythm control system. We are postulating another neural timer, i.e. the hippocampal theta rhythm. Cross-correlation between the R-wave of the electrocardiogram and the hippocampal theta revealed phase-locking during behavioral periods under 'open-loop' operations as paradoxical sleep indicative of a participation of such a rhythm in autonomic heart rate timing, in coordination with hypothalamic neuronal activities.

Changes in the cerebral blood flow in postlingual cochlear implant users.

Five postlingually deaf patients (age range 28-58 years) with multichannel cochlear implants were examined with single photon emission tomography (SPECT) (triple-head rotating gamma camera). Changes in the regional cerebral blood flow (rCBF) after intravenous administration of technetium-99m ethyl cysteinate dimer (Tc-99m ECD) were assessed through a stimulation paradigm, consisting of: i) click stimuli (75 dB SPL) in the ear that was to be implanted, 2 weeks before surgery; ii) stimulation with the same click, one month after initial fitting; iii) stimulation with hearing sequential Spanish sentences one month after initial fitting. The results showed a significant increase in the rCBF in the primary left auditory area and in the right auditory cortex, in conditions ii) and iii). The rCBF also showed a significant asymmetrical increase in the frontal lobes when the patient was hearing sequential sentences (condition iii)) with asymmetrical distribution among patients. These results are discussed, principally the correlation between speech discrimination scores and the rCBF distribution in the frontal and temporal lobes.

Membrane and circuit properties of lateral septum neurons: relationships with hippocampal rhythms.

The lateral septum receives the most important afferents from the hippocampus, has been proposed to contribute to theta (theta) rhythm generation. Our aim was to study the membrane and circuital properties of lateral septum neurons and their relationship with hippocampal rhythms. Extra- and intracellular recordings (n=81) were obtained in urethane-anesthetized rats. Two neuronal populations were found, one of them with hippocampal theta; rhythm dependence (theta-D, 68%), and the other group independent of hippocampal theta; rhythm (theta-I, 32%). Other differences were spontaneous firing rate (theta-D=13.20+/-2.09, theta-I=6.99+/-1.18; p<0.005) with a bursting pattern in the theta-D group and single discharges in the theta-I group. Intracellular recordings showed higher synaptic activity in theta-D than in theta-I neurons. Both groups showed fast spikes while only theta-D neurons had high-threshold and low-threshold slow spikes. theta-D neurons had theta-oscillations in their membrane potential. Stimulation of the contralateral lateral septum resets the hippocampal theta rhythm and the theta rhythm recorded intracellularly in the lateral septum neurons. Some neurons (10.6%) showed rhythmic oscillations lasting a few seconds, at a higher frequency than those of the simultaneously recorded hippocampal EEG. This high frequency appeared spontaneously or could be evoked by stimulations of the fornix and reticularis pontis oralis nucleus (RPO). Homologous high frequency oscillations appeared in the simultaneously recorded hippocampal EEG, synchronized with the neuronal activity, during fornix stimulation. RPO stimulation evoked increments (57%) or decrements (43%) in the firing rate of lateral septum neurons. Thus, they could participate in different septal networks to modulate the theta rhythm. The marked functional relationship between lateral septum neurons and hippocampal theta rhythm supports the proposal that lateral septum represents a feedback system for the improvement of medial septum theta rhythm. The hypothalamic projections could be a way to introduce theta and higher rhythms into this structure that control many biological rhythms.

Auditory cortical efferent actions upon inferior colliculus unitary activity in the guinea pig.

Differential actions on inferior colliculus central nucleus (ICc) single cells spontaneous activity were observed with both ipsilateral and contralateral auditory cortical electrical stimulation (ACx stimulation). Following ACx stimulation, a firing depression of the spontaneous activity was obtained using contralateral or ipsilateral cortical stimulation, although a greater effect was elicited by the contralateral cortex. In contrast, ipsilateral ACx stimulation elicited more excitation with a shorter latency than contralateral stimulation. In units that failed to show spontaneous firing, the sound-evoked responses and ACx stimulation were studied; approximately 50% of them demonstrated firing depression to ACx stimulation on either side with either clicks or tone-bursts. Thirty percent of the units failed to show changes in response to any cortical stimulation. A temporary disruption of ICc-evoked neuronal discharge was elicited during contralateral cortex stimulation, as previously reported to occur during sleep. The demonstration that auditory cortices may differentially affect the same ICc unit activity, i.e. spontaneous and evoked, suggests that auditory processing may depend on the ongoing spontaneous activity plus the effects exerted from each auditory cortex activation.

In vivo intracellular characteristics of inferior colliculus neurons in guinea pigs.

Intracellular in vivo recordings of physiologically identified inferior colliculus central nucleus (ICc) auditory neurons (n = 71) were carried out in anesthetized guinea pigs. The neuronal membrane characteristics are described showing mainly quantitative differences with a previous report [Nelson, P.G. and Erulkar, S.D., J. Neurophysiol., 26 (1963) 908-923]. The spontaneous spike activity was consistent with the discharge pattern of most extracellularly recorded units. The action potentials showed different spike durations, short and long, and some of them exhibited hyperpolarizing post-potentials. There were also differences in firing rate. The ICc neurons exhibited irregular activity producing spike trains as well as long silent periods (without spikes). Intracellular current injection revealed membrane potential adaptation and shifts that outlasted the electrical stimuli by 20-30 ms. Both evoked synaptic potentials and the spike activity in response to click and tone-burst stimulation were analyzed. Depolarizing-hyperpolarizing synaptic potentials were found in response to contralateral and binaural sound stimulation that far outlasted the stimulus (up to 90 ms). When ipsilaterally stimulated, inhibitory responses and no-responses were also recorded. Although few cells were studied, a similar phenomenon was observed using tone-burst stimulation; moreover, a good correlation was obtained between membrane potential shifts and the triggered spikes (input-output relationship). These in vivo results demonstrate the synaptic activity underlying many of the extracellularly recorded discharge patterns. The data are consistent with the known multi-synaptic ascending pathway by which signals arrive at the ICc as well as the descending corticofugal input that may contribute to the generation of long duration post-synaptic potentials.

Auditory deprivation modifies sleep in the guinea-pig.

After destruction of both cochleae, a significant enhancement of both paradoxical sleep and slow wave sleep together with decreased wakefulness, were observed for up to 45 days. The sleep augmentation consisted of an increment in the number of episodes of both slow wave and paradoxical sleep rather than in the duration of single episodes. The partial isolation provoked by deafness is postulated as explanation. We suggest that the suppression of one input to a complex set of networks related to the sleep-waking cycle, introduce an imbalance that leads to sleep enhancement.

Firing of inferior colliculus auditory neurons is phase-locked to the hippocampus theta rhythm during paradoxical sleep and waking.

The activity of 52 single auditory units in the central nucleus of the inferior colliculus (IC) was recorded along with cortical and hippocampal (CA1) electrograms and neck muscle electromyograms in behaving, head-restrained guinea pigs during paradoxical sleep (PS) and wakefulness. Sixteen (30%) of the IC auditory units showed positive correlation with the hippocampal theta (theta) rhythm: 8 (15%) were theta rhythmic with theta phase-locking (type 1), 8 (15%) showed only theta phase-locking with no rhythmicity (type 2), while 70% did not show any correlation to hippocampal theta rhythm (type 3). During wakefulness IC neurons (4 of 13) showed a higher synchrony with hippocampal theta when sound-stimulated at the unit's characteristic frequency. During PS all IC auditory neurons recorded presented some hippocampal theta correlation: 40% were rhythmic and phase-locked to the theta frequency and 60% were nonrhythmic maintaining the theta phase-locking. Shifts in the angle of phase-locking to the theta rhythm were observed during PS. It is suggested that the hippocampal theta rhythm may play the part of an internal clock, adding a temporal dimension to the processing of auditory sensory information.

Intracellular in vivo recording of inferior colliculus auditory neurons from awake guinea-pigs.

Intracellular recordings of identified inferior colliculus (ICc) auditory neurons, were analyzed in in vivo awake, chronically implanted guinea-pigs. The passive membrane characteristics as well as the spontaneous and click evoked synaptic potentials and spike activity, were studied. The injection of current pulses revealed little, if any, adaptation and membrane voltage shifts that outlasted the electrical stimuli. The spontaneous action potentials, observed in all the units studied, were of the short-duration type. During wakefulness, spontaneous synaptic potentials of higher amplitude were observed in comparison to the anesthetized preparation as well as an enhanced firing rate. The click evoked synaptic potentials far outlasted the sound (click, 0.1 ms) duration. The binaural, contralateral and ipsilateral sound stimulation evoked different sequences of synaptic potentials and firing. This was mostly in agreement with studies of extracellular recordings from the ICc, in anesthetized and behaving animals.

Effects of sleep on the responses of single cells in the lateral superior olive.

The effects of behavioral shifts on auditory lateral superior olive neurons were analyzed in guinea-pigs during the sleep-waking cycle with single unit extracellular recordings at the unit characteristic frequency and with low sound intensity. Shifts in the number of spikes in response to pure tones and in spontaneous firing proved to be closely related to waking, slow wave and paradoxical sleep. All of the recorded lateral superior olive (LSO) auditory neurons showed sleep-related firing shifts. Moreover, changes in the pattern of discharge over time were observed in 15% of the LSO cells on passing from waking to sleep. Sleep may determine either an increase or a decrease of the firing number in response to sound. The most important change observed in decreasing firing units was the near-absence of units responding to sound in the paradoxical sleep phase during the last 40 ms of the response. The waking cues for binaural detection, studied with our experimental paradigm, disappeared during slow wave sleep. We thus conclude that the binaural function of some lateral superior olive neurons (11.5%) was impaired during this sleep period in the present experimental conditions. Auditory efferent pathways are postulated to impinge on the auditory processing at LSO nucleus level during the sleep-waking cycle. Thus, auditory unitary activity appears to be dependent on both incoming information, and a CNS descending action closely related to the waking and sleep periods. Functional interactions between pontine sleep-related groups of neurons and auditory system units are suggested.

Internally-generated sound stimulates cochlear nucleus units.

The body generates many physiological sounds. One of the most prominent is that produced by the blood flowing inside the vessels with each heart beat. On the other hand, the cochlea is a very sensitive receptor with a low threshold. Given the anatomical close proximity of the carotid artery and other vessels to the inner ear, the possibility of its being stimulated is very high. Cochlear nucleus spontaneous as well sound-responding auditory units were studied. A close relationship between the heart beat, that is the blood flow, and the cochlear nucleus firing was demonstrated, in anesthetized and awake guinea-pigs. Temporary mechanical interruption of the blood flow through the ipsilateral carotid artery abolished firing increments at the cochlear nucleus time-locked to the heart beat. We conclude that one component of the so called 'spontaneous' firing in the auditory system is actually evoked activity due to normal body-generated sounds or noises.

Single unit activity in the guinea-pig cochlear nucleus during sleep and wakefulness.

The effects of waking and sleep on the response properties of auditory units in the ventral cochlear nucleus (CN) were explored by using extracellular recordings in chronic guinea-pigs. Significant increases and decreases in firing rate were detected in two neuronal groups, a) the "sound-responding" and b) the "spontaneous" (units that do not show responses to any acoustic stimuli controlled by the experimenter). The "spontaneous" may be considered as belonging to the auditory system because the corresponding units showed a suppression of their discharge when the receptor was destroyed. The auditory CN units were characterized by their PSTH in response to tones at their characteristic frequency and also by the changes in firing rate and probability of discharge evaluated during periods of waking, slow wave and paradoxical sleep. The CNS performs functions dependent on sensory inputs during wakefulness and sleep phases. By studying the auditory input at the level of the ventral CN with constant sound stimuli, it was shown that, in addition to the firing rate shifts, some units presented changes in the temporal probability of discharge, implying central actions on the corresponding neurons. The mean latency of the responses, however, did not show significant changes throughout the sleep-waking cycle. The auditory efferent pathways are postulated to modulate the auditory input at CN level during different animal states. The probability of firing and the changes in the temporal pattern, as shown by the PSTH, are thus dependent on both the auditory input and the functional brain state related to the sleep-waking cycle.

A search for a mesencephalic periaqueductal gray-cochlear nucleus connection.

Horseradish peroxidase placed into the ventral mesencephalic periaqueductal gray (PAG) and in the lateral superior olivary complex region demonstrated indirect paths towards the cochlear nucleus (CN). Because no direct connections could be observed, a pathway throughout the auditory efferent system was proposed. The results suggest three possibilities: 1) The PAG is connected to the lateral superior peri-olivary complex synapsing with known efferent fibers that reach the CN; 2) Neurons located at the dorsal PAG were demonstrated to be connected to the inferior colliculus (IC). The possibility of synapses with known neurons that run from IC to the CN is postulated; 3) Neurons in the trapezoid body, which are partially associated with a system that communicates with the CN, are also connected to and from the PAG. The present results anatomically support an extracellular study (1) describing PAG actions on CN units.

A search for a mesencephalic periaqueductal gray-cochlear nucleus connection.

Horseradish peroxidase placed into the ventral mesencephalic periaqueductal gray (PAG) and in the lateral superior olivary complex region demonstrated indirect paths towards the cochlear nucleus (CN). Because no direct connections could be observed, a pathway throughout the auditory efferent system was proposed. The results suggest three possibilities: 1) The PAG is connected to the lateral superior peri-olivary complex synapsing with known efferent fibers that reach the CN; 2) Neurons located at the dorsal PAG were demonstrated to be connected to the inferior colliculus (IC). The possibility of synapses with known neurons that run from IC to the CN is postulated; 3) Neurons in the trapezoid body, which are partially associated with a system that communicates with the CN, are also connected to and from the PAG. The present results anatomically support an extracellular study (1) describing PAG actions on CN units.

A search for a mesencephalic periaqueductal gray-cochlear nucleus connection.

Horseradish peroxidase placed into the ventral mesencephalic periaqueductal gray (PAG) and in the lateral superior olivary complex region demonstrated indirect paths towards the cochlear nucleus (CN). Because no direct connections could be observed, a pathway throughout the auditory efferent system was proposed. The results suggest three possibilities: 1) The PAG is connected to the lateral superior peri-olivary complex synapsing with known efferent fibers that reach the CN; 2) Neurons located at the dorsal PAG were demonstrated to be connected to the inferior colliculus (IC). The possibility of synapses with known neurons that run from IC to the CN is postulated; 3) Neurons in the trapezoid body, which are partially associated with a system that communicates with the CN, are also connected to and from the PAG. The present results anatomically support an extracellular study (1) describing PAG actions on CN units.

Periaqueductal gray influence on anteroventral cochlear nucleus unitary activity and naloxone effects.

The effect of periaqueductal gray (PAG) electrical stimulation on the response properties of auditory and 'spontaneously' firing units (abolished when the cochlea is destroyed) in the anteroventral cochlear nucleus (AVCN) was explored using extracellular recordings in acute guinea-pigs. Significant increases and decreases in firing rate were detected in both neuronal groups: only 4% of the sound-responding units were insensitive to PAG stimulation while the 'spontaneous' units showed significantly smaller changes in firing rate in response to PAG stimulation. The auditory AVCN neurons were categorized both by their sound post stimulus time (PST) histograms at their characteristic frequency (CF) and the changes in the probability of discharge after PAG stimulation while the tone burst was maintained constant. PAG was implicated in pain input modulation through enkephalin actions. Because enkephalins have been also observed at the CN level, a pharmacological approach administering naloxone was carried out. We observed that 1) naloxone abolished the unit discharge shifts observed after PAG stimulation and 2) when the drug was injected without PAG stimulation, it produced changes in the firing, increasing or decreasing, and shifts in the probability of discharge versus time, even in cases in which the firing rate was not altered. An involvement of the auditory efferent pathways to CN is postulated and a possible enkephalinergic factor is suggested as a modulator of the auditory input at this level. The probability of discharge observed in the PSTH at the AVCN is dependent on the auditory input plus the central efferent action to its neurons.

Correlative changes of auditory nerve and microphonic potentials throughout sleep.

Gross cochlear potentials in response to alternating clicks and pure tone bursts were recorded in guinea-pigs with chronically implanted electrodes in the round window during sleep and the awake state. A significant increase in both averaged potentials, the compound auditory nerve action potential (cAP) and cochlear microphonics (CM) occurred in slow wave sleep (SWS) with a subsequent diminution in paradoxical sleep (PS) periods. The cAP, CM, amplitude and area averages were similar during quiet wakefulness and in PS. Moreover, as an episode of PS progressed, the recorded potentials continued to decrease. On the other hand, increased averaged values were again observed during a subsequent episode of SWS. An involvement of the efferent olivo-cochlear bundle is postulated, first, because it is the only known pathway connecting the CNS and the auditory periphery and, second, because several key pre-receptor variables (middle ear muscles and ossicles and sound-source ear relation) were either abolished or altered dramatically.