Sleep-related neural activity in a premotor and a basal-ganglia pathway of the songbird

During singing, neurons in premotor nucleus RA (robust nucleus of the arcopallium) of the zebra finch produce complex temporal sequences of bursts that are recapitulated during sleep. RA receives input from nucleus HVC via the premotor pathway, and also from the lateral magnocellular nucleus of the anterior nidopallium (LMAN), part of a basal ganglia-related circuit essential for vocal learning. We explore the propagation of sleep-related spike patterns in these two pathways and their influences on RA activity. We promote sleep in head-fixed birds by injections of melatonin and make single-neuron recordings from the three major classes of neurons in HVC: RA-projecting neurons, Area X-projecting neurons, and interneurons. We also record LMAN neurons that project to RA. In paired recordings, spike trains from identified HVC neuron types are strongly coherent with spike trains in RA neurons, whereas LMAN projection neurons on average exhibit only a weak coherency with neurons in HVC and RA. We further examine the relative roles of HVC and LMAN in generating RA burst sequences with reversible inactivation. Lidocaine inactivation of HVC completely abolishes bursting in RA, whereas inactivation of LMAN has no effect on burst rates in RA. In combination, our data suggest that in adult birds, RA burst sequences in sleep are driven via the premotor pathway from HVC. We present a simple generative model of spike trains in HVC, RA, and LMAN neurons that is able to qualitatively reproduce observed coherency functions. We propose that commonly observed coherency peaks at positive and negative time lags are caused by sequentially correlated HVC activity.     

Singing-related activity of identified HVC neurons in the zebra finch

High vocal center (HVC) is part of the premotor pathway necessary for song production and is also a primary source of input to the anterior forebrain pathway (AFP), a basal ganglia-related circuit essential for vocal learning. We have examined the activity of identified HVC neurons of zebra finches during singing. Antidromic activation was used to identify three classes of HVC cells: neurons projecting to the premotor nucleus RA, neurons projecting to area X in the AFP, and putative HVC interneurons. HVC interneurons are active throughout the song and display tonic patterns of activity. Projection neurons exhibit highly phasic stereotyped firing patterns. X-projecting (HVC((X))) neurons burst zero to four times per motif, whereas RA-projecting neurons burst extremely sparsely--at most once per motif. The bursts of HVC projection neurons are tightly locked to the song and typically have a jitter of <1 ms. Population activity of interneurons, but not projection neurons, was significantly correlated with syllable patterns. Consistent with the idea that HVC codes for the temporal order in the song rather than for sound, the vocal dynamics and neural dynamics in HVC occur on different and uncorrelated time scales. We test whether HVC((X)) neurons are auditory sensitive during singing. We recorded the activity of these neurons in juvenile birds during singing and found that firing patterns of these neurons are not altered by distorted auditory feedback, which is known to disrupt learning or to cause degradation of song already learned.     

Sensorimotor nucleus NIf is necessary for auditory processing but not vocal motor output in the avian song system

Sensorimotor integration in the avian song system is crucial for both learning and maintenance of song, a vocal motor behavior. Although a number of song system areas demonstrate both sensory and motor characteristics, their exact roles in auditory and premotor processing are unclear. In particular, it is unknown whether input from the forebrain nucleus interface of the nidopallium (NIf), which exhibits both sensory and premotor activity, is necessary for both auditory and premotor processing in its target, HVC. Here we show that bilateral NIf lesions result in long-term loss of HVC auditory activity but do not impair song production. NIf is thus a major source of auditory input to HVC, but an intact NIf is not necessary for motor output in adult zebra finches.     

Temporal sparseness of the premotor drive is important for rapid learning in a neural network model of birdsong

Sparse neural codes have been widely observed in cortical sensory and motor areas. A striking example of sparse temporal coding is in the song-related premotor area high vocal center (HVC) of songbirds: The motor neurons innervating avian vocal muscles are driven by premotor nucleus robustus archistriatalis (RA), which is in turn driven by nucleus HVC. Recent experiments reveal that RA-projecting HVC neurons fire just one burst per song motif. However, the function of this remarkable temporal sparseness has remained unclear. Because birdsong is a clear example of a learned complex motor behavior, we explore in a neural network model with the help of numerical and analytical techniques the possible role of sparse premotor neural codes in song-related motor learning. In numerical simulations with nonlinear neurons, as HVC activity is made progressively less sparse, the minimum learning time increases significantly. Heuristically, this slowdown arises from increasing interference in the weight updates for different synapses. If activity in HVC is sparse, synaptic interference is reduced, and is minimized if each synapse from HVC to RA is used only once in the motif, which is the situation observed experimentally. Our numerical results are corroborated by a theoretical analysis of learning in linear networks, for which we derive a relationship between sparse activity, synaptic interference, and learning time. If songbirds acquire their songs under significant pressure to learn quickly, this study predicts that HVC activity, currently measured only in adults, should also be sparse during the sensorimotor phase in the juvenile bird. We discuss the relevance of these results, linking sparse codes and learning speed, to other multilayered sensory and motor systems.     

Regulation of learned vocal behavior by an auditory motor cortical nucleus in juvenile zebra finches

In the process of song learning, songbirds such as the zebra finch shape their initial soft and poorly formed vocalizations (subsong) first into variable plastic songs with a discernable recurring motif and then into highly stereotyped adult songs. A premotor brain area critically involved in plastic and adult song production is the cortical nucleus HVC. One of HVC's primary afferents, the nucleus interface of the nidopallium (NIf), provides a significant source of auditory input to HVC. However, the premotor involvement of NIf has not been extensively studied yet. Here we report that brief and reversible pharmacological inactivation of NIf in juvenile birds leads to transient degradation of plastic song toward subsong, as revealed by spectral and temporal song features. No such song degradation is seen following NIf inactivation in adults. However, in both juveniles and adults NIf inactivation leads to a transient decrease in song stereotypy. Our findings reveal a contribution of NIf to song production in juveniles that agrees with its known role in adults in mediating thalamic drive to downstream vocal motor areas during sleep.     

Changes in the neural control of a complex motor sequence during learning

The acquisition of complex motor sequences often proceeds through trial-and-error learning, requiring the deliberate exploration of motor actions and the concomitant evaluation of the resulting performance. Songbirds learn their song in this manner, producing highly variable vocalizations as juveniles. As the song improves, vocal variability is gradually reduced until it is all but eliminated in adult birds. In the present study we examine how the motor program underlying such a complex motor behavior evolves during learning by recording from the robust nucleus of the arcopallium (RA), a motor cortex analog brain region. In young birds, neurons in RA exhibited highly variable firing patterns that throughout development became more precise, sparse, and bursty. We further explored how the developing motor program in RA is shaped by its two main inputs: LMAN, the output nucleus of a basal ganglia-forebrain circuit, and HVC, a premotor nucleus. Pharmacological inactivation of LMAN during singing made the song-aligned firing patterns of RA neurons adultlike in their stereotypy without dramatically affecting the spike statistics or the overall firing patterns. Removing the input from HVC, on the other hand, resulted in a complete loss of stereotypy of both the song and the underlying motor program. Thus our results show that a basal ganglia-forebrain circuit drives motor exploration required for trial-and-error learning by adding variability to the developing motor program. As learning proceeds and the motor circuits mature, the relative contribution of LMAN is reduced, allowing the premotor input from HVC to drive an increasingly stereotyped song.     

Synaptic interactions underlying song-selectivity in the avian nucleus HVC revealed by dual intracellular recordings

Stimulus-dependent synaptic interactions underlying selective sensory representations in neural circuits specialized for sensory processing and sensorimotor integration remain poorly understood. The songbird telencephalic nucleus HVC is a sensorimotor area essential to learned vocal control with one projection neuron (PN) type (HVC(RA)) innervating a song premotor pathway, another PN (HVC(X)) innervating a basal ganglia pathway essential to vocal plasticity, and interneurons (HVC(Int)). Playback of the bird's own song (BOS), but not other songs, evokes action potential bursts from both PNs, but HVC(RA) and HVC(X) display distinct BOS-evoked subthreshold responses. To characterize synaptic interactions underlying HVC's BOS-selective responses and assess stimulus-evoked changes in functional interactions between HVC neurons, we made simultaneous in vivo intracellular recordings from various HVC neuron pairs in urethan-anesthetized zebra finches. Spike-triggered averaging revealed that all HVC neuron types receive common excitation and that the onset of this excitation occurs during a narrower time window in projection neurons during BOS playback. To distinguish local from extrinsic contributions to HVC subthreshold response patterns, we inactivated the HVC local circuit with GABA or occluded inhibition in single HVC(X) cells. After either treatment, BOS-evoked responses in HVC(X) neurons became purely depolarizing and subthreshold responses of HVC(X) and HVC(RA) cells became remarkably similar to one another while retaining BOS selectivity. Therefore both PN types receive a common extrinsic source of BOS-selective excitation, and local inhibition specifically alters processing of auditory information in HVC(X) cells. In HVC, excitatory and inhibitory synaptic interactions are recruited in a stimulus-dependent fashion, affecting auditory representations of the BOS locally and in other song nuclei important to song learning and production.     

Long-range inhibition within the zebra finch song nucleus RA can coordinate the firing of multiple projection neurons.

The zebra finch forebrain song control nucleus RA (robust nucleus of the archistriatum) generates a phasic and temporally precise neural signal that drives vocal and respiratory motoneurons during singing. RA's output during singing predicts individual notes, even though afferent drive to RA from the song nucleus HVc is more tonic, and predicts song syllables, independent of the particular notes that comprise the syllable. Therefore RA's intrinsic circuitry transforms neural activity from HVc into a highly precise premotor output. To understand how RA's intrinsic circuitry effects this transformation, we characterized RA interneurons and projection neurons using intracellular recordings in brain slices. RA interneurons fired fast action potentials with steep current-frequency relationships and had small somata with thin aspinous processes that extended throughout large portions of the nucleus; the similarity of their fine processes to those labeled with a glutamic acid decarboxylase (GAD) antibody strongly suggests that these interneurons are GABAergic. Electrical stimulation revealed that RA interneurons receive excitatory inputs from RA's afferents, the lateral magnocellular nucleus of the anterior neostriatum (LMAN) and HVc, and from local axon collaterals of RA projection neurons. To map the functional connections that RA interneurons make onto RA projection neurons, we focally uncaged glutamate, revealing long-range inhibitory connections in RA. Thus these interneurons provide fast feed-forward and feedback inhibition to RA projection neurons and could help create the phasic pattern of bursts and pauses that characterizes RA output during singing. Furthermore, selectively activating the inhibitory network phase locks the firing of otherwise unconnected pairs of projection neurons, suggesting that local inhibition could coordinate RA output during singing.     

Auditory responses in multiple sensorimotor song system nuclei are co-modulated by behavioral state

Auditory responsiveness in nucleus HVC, a high-order sensorimotor area of the avian song system, is modulated by changes in behavioral state. Modulation is not observed in the primary thalamo-recipient auditory area Field L, the indirect source of auditory input to HVC. In this study, we show that auditory responsiveness in nucleus interfacialis (NIf), the immediate auditory afferent to HVC, is modulated by behavioral state. While auditory responsiveness is generally greater in NIf during wakefulness and in HVC during sedation, simultaneous recordings reveal a co-variation of auditory response magnitude. This co-variation is observed both in awake birds, where responses are spontaneously variable, and in sedated birds during manipulations of arousal levels. Auditory responses in NIf and HVC, which are selective for the bird's own song (BOS) during sedation, become predominantly unselective during wakefulness. This loss of selectivity is accompanied by a decrease in the similarity of NIf and HVC response patterns. To explore the role of NIf in shaping HVC auditory responses, we pharmacologically manipulated NIf while recording in HVC. Injection of the GABA(A) agonist muscimol into NIf eliminated most spontaneous activity and all auditory responses in the ipsilateral HVC, while injections of the GABA(A) antagonist bicuculline increased HVC auditory responsiveness and selectivity. These findings indicate that HVC is not the initial site of behavioral state-dependent modulation in the song system. Together with the suppression of HVC auditory responses by muscimol in NIf, these results suggest that NIf plays an important role in the flow of auditory information to HVC.     

Revisiting the reticulum: feedforward and feedback contributions to motor program parameters in the crab cardiac ganglion microcircuit

The neurogenic heartbeat of crustaceans is controlled by the cardiac ganglion (CG), a central pattern generator (CPG) microcircuit composed of nine neurons. In most decapods, five "large" motor neurons (MNs) project from the CG to the myocardium, where their excitatory synaptic signals generate the rhythmic heartbeat. The processes of four "small" premotor neurons (PMNs) are confined to the CG, where they provide excitatory drive to the MNs via impulse-mediated chemical signals and electrotonic coupling. This study explored feedforward and feedback interactions between the PMNs and the MNs in the CG of the blue crab (Callinectes sapidus). Three methods were used to compare the activity of the MNs and the PMNs in the integrated CG to their autonomous firing patterns: 1) ligatures were tightened on the ganglion trunk that connects the PMNs and MNs; 2) TTX was applied focally to suppress selectively PMN or MN activity; and 3) sucrose pools were devised to block reversibly PMN or MN impulse conduction. With all treatments, the PMNs and MNs continued to produce autonomous rhythmic bursting following disengagement. Removal of PMN influence resulted in a significantly reduced MN duty cycle that was mainly attributable to a lower autonomous burst frequency. Conversely, after removal of MN feedback, the PMN duty cycle was increased, primarily due to a prolonged burst duration. Application of sucrose to block impulse conduction without eliminating PMN oscillations disclosed significant contributions of spike-mediated PMN-to-MN signals to the initiation and prolongation of the MN burst. Together, these observations support a view of the Callinectes CG composed of two classes of spontaneously bursting neurons with distinct endogenous rhythms. Compartmentalized feedforward and feedback signaling endow this microcircuit with syncytial properties such that the intrinsic attributes of the PMNs and MNs both contribute to shaping all parameters of the motor patterns transmitted to the myocardium.     

Noradrenergic and GABA B receptor activation differentially modulate inputs to the premotor nucleus RA in zebra finches

Neuromodulators can rapidly modify neural circuits, altering behavior. Songbirds provide an excellent system for studying the role of neuromodulation in modifying circuits that underlie behavior because song learning and production are mediated by a discrete set of interconnected nuclei. We examined the neuromodulatory effects of noradrenergic and GABA B receptor activation on synaptic inputs to the premotor robust nucleus of the arcopallium (RA) in zebra finches using whole cell voltage-clamp recording in vitro. In adults, norepinephrine strongly reduced input from the lateral magnocellular nucleus of the anterior nidopallium (LMAN) but only slightly reduced the input from nucleus HVC (proper name), the excitatory input from axon collaterals of other RA neurons, and input from GABAergic interneurons. The effect of norepinephrine was mimicked by the alpha2 adrenoceptor agonist UK14,304 and blocked by the alpha2 antagonist yohimbine. Conversely, the GABA B receptor agonist baclofen strongly decreased HVC, collateral, and GABAergic inputs to RA neurons while causing little reduction in the LMAN input. In juveniles undergoing song learning, norepinephrine reduced the LMAN input, caused only a small reduction in the HVC input, and greatly reduced the collateral and GABAergic inputs. Baclofen caused similar results in juvenile and adult birds, reducing HVC, collateral, and GABAergic inputs significantly more than the LMAN input. Significant increases in paired-pulse ratio accompanied all reductions in synaptic transmission, suggesting a presynaptic locus. The reduction in the LMAN input by norepinephrine may be important for mediating changes in song elicited by different social contexts and is well-placed to play a role in song learning.     

黄眉鹀(Emberiza Chrysophrys)端脑发声控制核团的传入投射——HRP法研究

本文用HRP顺、逆行追踪方法,研究了黄眉鹀端脑发声控制中枢-上纹状体腹侧尾核及古纹状体粗核的传入投射。将HRP微电泳入上纹状体腹侧尾核,在同侧新纹状体前部巨细胞核的内侧部、新纹状体中部界面核、端脑听区-Field L、丘脑Uvacformis核及脑桥蓝斑等处见到密布的标记细胞,在古纹状体粗核及嗅叶的X区等处出现了密集成簇的标记终末。将HRP微电泳入古纹状体粗核,逆行标记细胞分布于同侧上纹状体腹侧尾核、新纹状体前部巨细胞核的外侧部、古纹状体带核及蓝斑等处。上述结果表明,上纹状体腹侧尾核接受新纹状体的前部巨细胞核内侧部、新纹状体中部界面核、端脑听区-Field L、丘脑Uvacformis核及脑桥蓝斑的传入投射。新纹状体前部巨细胞核、新纹状体中部界面核和Uvacformis核是参与发声学习与记忆的核团,L区是听觉的最高位中枢,蓝斑与植物性以及情绪性反应有关。提示上纹状体腹侧尾核也参与发声学习、听觉记忆以及植物性、情绪性反应的调节。古纹状体粗核接受上纹状体腹侧尾核、新纹状体前部巨细胞核外侧部、古纹状体带核及蓝斑的传入投射。     

Burst and tonic response modes in thalamic neurons during sleep and wakefulness

Thalamic neurons can exhibit two distinct firing modes: tonic and burst. In the lateral geniculate nucleus (LGN), the tonic mode appears as a relatively faithful relay of visual information from retina to cortex. The function of the burst mode is less understood. Its prevalence during slow-wave sleep (SWS) and linkage to synchronous cortical electroencephalogram (EEG) suggest that it has an important role during this form of sleep. Although not nearly as common, bursting can also occur during wakefulness. The goal of this study was to identify conditions that affect burst probability, and to compare burst incidence during sleeping and waking. LGN neurons are extraordinarily heterogenous in the degree to which they burst, during both sleeping and waking. Some LGN neurons never burst under any conditions during wakefulness, and several never burst during slow-wave sleep. During wakefulness, <1% of action potentials were associated with bursting, whereas during sleep this fraction jumps to 18%. Although bursting was most common during slow-wave sleep, more than 50% of the bursting originated from 14% of the LGN cells. Bursting during sleep was largely restricted to episodes lasting 1-5 s, with approximately 47% of these episodes being rhythmic and in the delta frequency range (0.5-4 Hz). In wakefulness, although visual stimulation accounted for the greatest number of bursts, it was still a small fraction of the total response (4%, 742 bursts/17,744 cycles in 93 cells). We identified two variables that appeared to influence burst probability: size of the visual stimuli used to elicit responses and behavioral state. Increased stimulus size increased burst probability. We attribute this to the increased influence large stimuli have on a cell's inhibitory mechanisms. As with sleep, a large fraction of bursting originated from a small number of cells. During visual stimulation, 50% of bursting was generated by 9% of neurons. Increased vigilance was negatively correlated with burst probability. Visual stimuli presented during active fixation (i.e., when the animal must fixate on an overt fixation point) were less likely to produce bursting, than when the same visual stimuli were presented but no fixation point present ("passive" fixation). Such observations suggest that even brief departures from attentive states can hyperpolarize neurons sufficiently to de-inactivate the burst mechanism. Our results provide a new view of the temporal structure of bursting during slow-wave sleep; one that supports episodic rhythmic activity in the intact animal. In addition, because bursting could be tied to specific conditions within wakefulness, we suggest that bursting has a specific function within that state.     

Behavioral state-dependent reconfiguration of song-related network activity and cholinergic systems

The song system of oscine songbirds mediates multiple complex perceptive and productive behaviors. These discrete behaviors are modulated according to external variables such as social context, directed attention and other forms of experience. In addition, sleep has been implicated in song learning and song maintenance. Changes in behavioral state are associated with complex changes in auditory responsiveness and tonic/bursting properties of song system neurons. Cholinergic input, principally from the basal forebrain has been implicated in some of these state-dependent properties. Cholinergic modulation may affect numerous song system nuclei, with in vivo and in vitro studies indicating that a major target of cholinergic input is the forebrain nucleus HVC. Within HVC, a muscarinic cholinergic system has strong regulatory effects on most neurons, and may serve to couple and uncouple circuitry within HVC projecting along the premotor pathway with circuitry within HVC projecting along the cortico-basal ganglia pathway. These observations begin to describe how neuromodulatory regulation in the song system may contribute to learning phenomena.     

Young,active and well-connected: adult-born neurons in the zebra finch are activated during singing

Neuronal replacement in the pallial song control nucleus HVC of adult zebra finches constitutes an interesting case of homeostatic plasticity; in spite of continuous addition and attrition of neurons in ensembles that code song elements, adult song remains remarkably invariant. New neurons migrate into HVC and later synapse with their target, arcopallial song nucleus RA (HVC_RA). New HVC_RA neurons respond to auditory stimuli (in anaesthetised animals), but whether and when they become functionally active during singing is unknown. We studied this, using 5-bromo-2′-deoxyuridine to birth-date neurons, combined with immunohistochemical detection of immediate-early gene (IEG) expression and retrograde tracer injections into RA to track connectivity. Interestingly, singing was followed by IEG expression in a substantial fraction of new neurons that were not retrogradely labelled from RA, suggesting a possible role in HVC-intrinsic network function. As new HVC neurons matured, the proportion of HVC_RA neurons that expressed IEGs after singing increased significantly. Since it was previously shown that singing induces IEG expression in HVC also in deaf birds and that hearing song does not induce IEG expression in HVC, our data provide the first direct evidence that new HVC neurons are engaged in song motor behaviour.     

Stimulation of the pedunculopontine tegmental nucleus in the rat produces burst firing in A9 dopaminergic neurons.

Stimulation of the medial prefrontal cortex in the rat produces events in midbrain dopaminergic neurons which resemble natural bursts, and which are closely time-locked to the stimulation, albeit with a very long latency. As a consequence, we have previously argued that such bursts are polysynaptically generated via more proximal excitatory amino acidergic afferents, arising, for example, from the pedunculopontine tegmental nucleus. In the present study, single-pulse electrical stimulation applied to this nucleus (and other sites in the rostral pons) was found to elicit responses in the majority of substantia nigra (A9) dopaminergic neurons. Responses usually consisted of long-latency, long-duration excitations or inhibition-excitations. Thirty-seven percent of responses (currents combined) elicited by stimulation of the pedunculopontine tegmental nucleus contained time-locked bursts, the bursts being embedded in the long-duration excitatory phases of excitation and inhibition-excitation responses. Stimulation sites located within 0.5 mm of the pedunculopontine tegmental nucleus were also effective at eliciting time-locked bursts (although less so than sites located in the nucleus itself), whereas more distal sites were virtually ineffective. For responses containing time-locked bursts, a higher percentage of stimulations produced a burst when the response was elicited from within the pedunculopontine tegmental nucleus than when it was elicited from outside: the bursts themselves having a very long latency (median of 96.2 ms; shorter than that of medial prefrontal cortex-induced bursts). Finally, although there was no difference in the distribution within the substantia nigra pars compacta of cells which exhibited time-locked bursting and those which did not, stimulation-induced bursts were elicited more frequently in dopaminergic neurons which were classified as "bursting" on the basis of their basal activity. The pedunculopontine tegmental nucleus appears to be a critical locus in the rostral pons for the elicitation of time-locked bursts in A9 dopaminergic neurons. Since time-locked bursts were more often elicited from cells which exhibited bursting under basal conditions, this suggests that rostral pontine sites, in particular the pedunculopontine tegmental nucleus, may play a role in the natural burst activity of dopaminergic neurons. Given that bursts in dopaminergic neurons are generated in response to primary and secondary reinforcers, the projection from the pedunculopontine tegmental nucleus could be one means by which motivationally relevant information (arising, for example, from the medial prefrontal cortex) reaches these cells.     

Functional organization of premotor neurons in the cat medial vestibular nucleus related to slow and fast phases of nystagmus

Summary Extracellular spikes were recorded from secondary vestibular neurons in the cat medial vestibular nucleus (MVN) and were identified as type I or II neurons by horizontal rotation. Type I neurons were further classified as excitatory or inhibitory premotor neurons on the basis of their axonal termination in the contralateral or ipsilateral abducens nucleus, demonstrated by spike-triggered averaging of abducens nerve discharges, or by antidromic activation using systematic microstimulation within the abducens nucleus.Both excitatory and inhibitory premotor type I MVN neurons exhibited a rhythmic modulation of their firing rate in association with nystagmus elicited by rotation or electrical stimulation of the vestibular nerve. Their tonic activity during the slow phase was suppressed at the quick phase directed to the ipsilateral side.Excitatory type I MVN neurons terminating in the contralateral abducens nucleus sent collateral axons to the contralateral MVN. These commissural neurons also showed a nystagmus-related discharge pattern.Type II MVN neurons activated at short latency by stimulation of the contralateral vestibular nerve exhibited burst discharges when the activity of ipsilateral type I neurons was suppressed at the quick phase. These type II neurons made monosynaptic inhibitory connections with type I neurons as shown by the post-spike average of the membrane potential of secondary MVN neurons triggered from spikes of single type II neurons. Thus, the inhibitory action originating from burst activity of type II MVN neurons contributes to suppression of type I premotor MVN neurons during fast eye movements.Supported by Grant-in-Aid for Scientific Research No. 248106 from Japan Ministry of Education, Science and Culture. Dr. Schor was supported by the Research Fellowship of Japan Society for the Promotion of Science (JSPS)     

Developmental modulation of the temporal relationship between brain and behavior

Humans and songbirds shape learned vocalizations during a sensorimotor sensitive period or "babbling" phase. The brain mechanisms that underlie the shaping of vocalizations by sensory feedback are not known. We examined song behavior and brain activity in zebra finches during singing as they actively shaped their song toward a tutor model. We now show that the temporal relationship of behavior and activity in the premotor area HVC changes with the development of song behavior. During sensorimotor learning, HVC bursting activity both preceded and followed learned vocalizations by hundreds of milliseconds. Correspondingly, the duration of bursts that occurred during ongoing song motif behavior was prolonged in juveniles, as compared with adults, and was inversely correlated with song maturation. Multielectrode single-unit recording in juveniles revealed that single fast-spiking neurons were active both before and after vocalization. These same neurons responded to auditory stimuli. Collectively, these data indicate that a key aspect of sensory critical periods--prolonged bursting--also applies to sensorimotor development. In addition, prolonged motor discharge and sensory input coincide in single neurons of the developing song system, providing the necessary cellular elements for sensorimotor shaping through activity-dependent mechanisms.     

Hypoglossal premotor neurons with rhythmical inspiratory-related activity in the cat: localization and projection to the phrenic nucleus

Localization and projection to the phrenic (PH) nucleus were studied in a sample of premotor neurons that directly projected to hypoglossal motoneurons (XII Mns) and showed respiratory-related patterns of activity. The experiments were carried out in cats, under pentobarbital anesthesia. In the first part of the study, the retrograde double-labeling technique was used to reveal the existence of neurons projecting to both the XII and the PH nuclei. Injection of a fluorescent dye (fast blue, FB) into the XII nucleus and another (nuclear yellow, NY) into the PH nucleus retrogradely labeled, with either FB or NY, medullary reticular neurons mainly in the regions ventrolateral to the nucleus of the tractus solitarius (vl-NTS), ventrolateral to the hypoglossal nucleus (vl-XII), and dorsomedial to the nucleus ambiguus (dm-AMB) bilaterally. In addition, some neurons in these regions were labeled with both FB and NY. In the second part of the study, unitary activity was recorded extracellularly from medullary respiratory neurons. In the regions vl-NTS, vl-XII, and dm-AMB, inspiratory neurons were found which antidromically responded to stimulation of the XII nucleus. Some of them also responded antidromically to stimulation of the PH nucleus. Averaging of rectified and integrated XII and PH nerve discharges by spontaneous spikes of single inspiratory neurons in the vl-NTS and dm-AMB regions revealed a facilitation in either XII nerve discharge or both XII and PH nerve discharges after a short latency of monosynaptic range. It is concluded that in the vl-NTS and dm-AMB regions there are inspiratory neurons that are excitatory premotor neurons projecting to XII Mns showing the respiratory-related activity. Some of them have excitatory synaptic connections to XII and PH Mns via bifurcating axons.     

小鼠脑干交感运动前区前阿黑皮素能神经传入投射的实验研究

目的:研究脑干交感运动前区的前阿黑皮素能神经纤维的分布及其传入投射。方法:以免疫组化法检测前阿黑皮素能神经纤维在脑干交感运动前区的分布;将霍乱毒素B微量注入小鼠脑干交感运动前区进行逆行追踪。结果:α-MSH(α-melanocyte-stimulating hormone)能神经终末密集分布于交感运动前区内,同时则未见AgRP(agouti-related protein)能神经终末,显示交感运动前区仅接受前阿黑皮素(POMC)能神经的单向调节。逆行追踪实验显示脑干交感运动前区的POMC能纤维投射来自于下丘脑弓状核/视交叉后区,而非孤束核尾侧部;统计结果表明下丘脑弓状核/视交叉后区向脑干交感运动前区的神经投射中有近一半为POMC能投射。结论:小鼠下丘脑的POMC能神经元可直接投射到脑干交感运动前区,该神经通路在能量平衡的调节中可能发挥重要的作用。