Midbrain Pathways Research Articles

Auditory Spatial Tuning at the Crossroads of the Midbrain and Forebrain

The barn owl's midbrain and forebrain contain neurons tuned to sound direction. The spatial receptive fields of these neurons result from sensitivity to combinations of interaural time (ITD) and level (ILD) differences over a broad frequency range. While a map of auditory space has been described in the midbrain, no similar topographic representation has been found in the forebrain. The first nuclei that belong exclusively to the forebrain and midbrain pathways are the thalamic nucleus ovoidalis (Ov) and the external nucleus of the inferior colliculus (ICx), respectively. The midbrain projects to the auditory thalamus before sharp spatial receptive fields emerge; although Ov and ICx receive projections from the same midbrain nuclei, they are not directly connected. We compared the spatial tuning in Ov and ICx. Thalamic neurons respond to a broader frequency range and their ITD and ILD tuning varied more across frequency. However, neurons in Ov showed spatial receptive fields as selective as neurons in ICx. Thalamic spatial receptive fields were tuned to frontal and contralateral space and correlated with their tuning to ITD and ILD. Our results indicate that spatial tuning emerges in both pathways by similar combination selectivity to ITD and ILD. However, the midbrain and the thalamus do not appear to repeat exactly the same processing, as indicated by the difference in frequency range and the broader tuning to binaural cues. The differences observed at the initial stages of these sound-localization pathways may reflect diverse functions and coding schemes of midbrain and forebrain.

Tuning to Interaural Time Difference and Frequency Differs Between the Auditory Arcopallium and the External Nucleus of the Inferior Colliculus

Barn owls process sound-localization information in two parallel pathways, the midbrain and the forebrain pathway. Exctracellular recordings of neural responses to auditory stimuli from far advanced stations of these pathways, the auditory arcopallium in the forebrain and the external nucleus of the inferior colliculus in the midbrain, demonstrated that the representations of interaural time difference and frequency in the forebrain pathway differ from those in the midbrain pathway. Specifically, low-frequency representation was conserved in the forebrain pathway, while it was lost in the midbrain pathway. Variation of interaural time difference yielded symmetrical tuning curves in the midbrain pathway. By contrast, the typical forebrain-tuning curve was asymmetric with a steep slope crossing zero time difference and a less-steep slope toward larger contralateral time disparities. Low sound frequencies contributed sensitivity to contralateral leading sounds underlying these asymmetries, whereas high frequencies enhanced the steepness of slopes at small interaural time differences. Furthermore, the peaks of time-disparity tuning curves were wider in the forebrain than in the midbrain. The distribution of the steepest slopes of best interaural time differences in the auditory arcopallium, but not in the external nucleus of the inferior colliculus, was centered at zero time difference. The distribution observed in the auditory arocpallium is reminiscent of the situation observed in small mammals. We speculate that the forebrain representation may serve as a population code supporting fine discrimination of central interaural time differences and coarse indication of laterality of a stimulus for large interaural time differences.

Midbrain pathways for prepulse inhibition and startle activation in rat

The midbrain is essential for prepulse inhibition (PPI) of the startle reflex, but the exact neural circuits for PPI are not yet determined. Electrical stimulation of the superior colliculus (SC) or pedunculopontine tegmentum was used to characterize the neurons and pathways that mediate PPI and the activation of startle that also occurs at higher currents in the same sites. Startle was inhibited by prepulses in most, but not all SC sites, with the lowest intensity sites in intermediate layers of SC. PPI latencies in SC sites were 4–6 ms longer than in inferior colliculus, intercollicular nucleus or pedunculopontine sites. Contrary to previous serial models, there must be two parallel midbrain pathways for PPI, a faster auditory pathway from inferior colliculus to pedunculopontine tegmentum, and a slower multimodal SC output for PPI. Double-pulse stimulation of SC sites shows that PPI results from direct stimulation of neurons with moderate refractory periods (0.4–1.0 ms), similar to SC neurons that mediate contraversive turning responses. By contrast, startle activation occurring at higher currents in all SC sites (even sites where PPI could not be elicited) results from stimulation of very short refractory period neurons (0.3–0.5 ms) and very long refractory period neurons (1.0–2.0 ms), with startle inhibition often found from 0.5–1.0 ms. Startle activation appears to result from stimulation of short refractory period neurons in deep SC layers that mediate fear-potentiated startle, plus long refractory period substrates in more dorsal SC sites.

Prefrontal Cortical Projections to the Midbrain in Primates: Evidence for a Sparse Connection

Frontal cortical efferent fibers are thought to have important regulatory influence on cortico-basal ganglia (BG) circuits. The cortico-midbrain (substantia nigra/ventral tegmental area, SN/VTA) pathway has received particular attention in psychiatric diseases, most notably schizophrenia. Work in rodents demonstrates that the prefrontal cortico (PFC)-midbrain pathway plays a central role in regulating the firing pattern of dopamine (DA) neurons. These findings have led to some important hypotheses concerning PFC/BG interaction in schizophrenia. Descending PFC projections to the SN/VTA have been primarily documented in the rodent. The aim of this study was to determine the degree and organization of PFC afferents to these areas in the Macaque monkey. Anterograde tracer injections were made into discrete orbital, cingulate, and dorsolateral prefrontal areas. Projections were charted to the SN and VTA. Overall, there were very few fibers in the ventral midbrain following injections confined to specific areas of the PFC. To determine the relationship of the descending fibers to the midbrain DA neurons, sections were double stained for the tracer molecules and for tyrosine hydroxylase. In all cases, the prefrontal projections and the TH-positive cells did not appear to be in close juxtaposition. The results show a very limited projection from the PFC to the midbrain DA neurons in primates, terminating both within the SN proper as well as in the VTA. They arise from a broad region of the PFC, including the DLPF, cingulate, and orbital cortices. However, despite the relative lack of cortical input to the midbrain cells, these neurons are rich in glutamate receptors in primates. Thus, while, based on these anatomical studies, direct cortical control of DA neurons remains debatable in primates; the cortex may directly impact other sources of glutamatergic control.

Rapid, hierarchical modulation of vocal patterning by steroid hormones.

Vocal control systems have been identified in all major groups of jawed vertebrates. Although steroid hormones are instrumental in the long-term development and maintenance of neural structures underlying vocalization, it is unknown whether steroids rapidly modulate the neural activity of vocal motor systems. The midshipman fish generates advertisement and agonistic calls that mainly differ in duration. A descending midbrain pathway activates a hindbrain-spinal vocal circuit that directly establishes the discharge frequency and duration of the rhythmic vocal motor volley. This vocal motor output, which can be monitored from occipital nerve roots, directly determines the rate and duration of contraction of a pair of sonic muscles and, in turn, the fundamental frequency and duration of vocalizations. Here, we demonstrate that the duration of the vocal motor volley, or fictive vocalization, is rapidly responsive to steroid hormones, including androgens, estrogens, and glucocorticoids. These responses are consistent, in part, with a nongenomic mechanism and are steroid specific at the receptor level, suggesting the possibility of multiple membrane-bound receptor populations. We also show, using intact and semi-intact preparations, that steroids hierarchically modulate fictive vocalizations; whereas the hindbrain-spinal region is both necessary and sufficient for rapid (within 5 min) effects on duration, descending midbrain input is necessary for maintenance (up to 120 min) of these effects. The conserved nature of vertebrate vocal motor systems suggests that the neuroendocrine principles outlined in this study may be a fundamental feature of all vocal vertebrates.

Early Visual Experience Shapes the Representation of Auditory Space in the Forebrain Gaze Fields of the Barn Owl

Auditory spatial information is processed in parallel forebrain and midbrain pathways. Sensory experience early in life has been shown to exert a powerful influence on the representation of auditory space in the midbrain space-processing pathway. The goal of this study was to determine whether early experience also shapes the representation of auditory space in the forebrain. Owls were raised wearing prismatic spectacles that shifted the visual field in the horizontal plane. This manipulation altered the relationship between interaural time differences (ITDs), the principal cue used for azimuthal localization, and locations of auditory stimuli in the visual field. Extracellular recordings were used to characterize ITD tuning in the auditory archistriatum (AAr), a subdivision of the forebrain gaze fields, in normal and prism-reared owls. Prism rearing altered the representation of ITD in the AAr. In prism-reared owls, unit tuning for ITD was shifted in the adaptive direction, according to the direction of the optical displacement imposed by the spectacles. Changes in ITD tuning involved the acquisition of unit responses to adaptive ITD values and, to a lesser extent, the elimination of responses to nonadaptive (previously normal) ITD values. Shifts in ITD tuning in the AAr were similar to shifts in ITD tuning observed in the optic tectum of the same owls. This experience-based adjustment of binaural tuning in the AAr helps to maintain mutual registry between the forebrain and midbrain representations of auditory space and may help to ensure consistent behavioral responses to auditory stimuli.

Wyburn–Mason Syndrome Variant Treated with Stereotactic Radiosurgery

Classical Wyburn–Mason syndrome consists of unilateral arteriovenous malformations affecting the retina, midbrain, and visual pathways in the brain, and the facial structures. An unusual case of Wyburn–Mason syndrome with bilateral manifestations and without retinal involvement is described. A 19-year-old girl presented at the age of 5 with a left hemiparesis and aphasia following intracerebral hemorrhage in the right internal capsule and basal ganglia. Angiography demonstrated left sylvian, right frontoparietal, and right thalamic arteriovenous malformations (AVMs). In addition to multiple intracranial AVMs, she had multiple telangiectatic lesions scattered over her body. Ophthalmological examination was normal except for left orbital bruit. Two years later, with moderate clinical improvement, she had proton beam radiosurgery for her multiple AVMs. Due to lack of beneficial effect, repeat radiosurgery with more appropriate dose is under consideration. A review of the literature revealed that our presenting case represents one of the few reported cases of atypical Wyburn–Mason syndrome with bilateral manifestations and without retinal involvement. To our knowledge, ours represent the first reported case for which radiosurgery had been offered as a treatment modality.

The effects of combined superior temporal polysensory area and frontal eye field lesions on eye movements in the macaque monkey

We previously found [42] that lesions of the superior temporal polysensory area (STP) cause temporary deficits in the production of eye movements. In order to both define regions participating in the ensuing recovery and to further explore the cortical control of eye movements, we examined the effects of addition of frontal eye field (FEF) lesions to STP lesions, on visual fixation, saccadic eye movements, and smooth pursuit eye movements. Three monkeys received bilateral STP lesions followed by a FEF lesion and as a control, an additional monkey received a bilateral inferior temporal cortex (IT) lesion followed by a FEF lesion. All animals had a profound impairment in foveating the central fixation point. This impairment was completely eliminated by turning on a dim light in the testing chamber. Large neglect-like impairments in making saccades were only seen after combined STP and FEF lesions. Impairments in making smooth pursuit eye movements after combined lesions of STP and FEF were larger than those seen after STP lesions but within the range of deficits that have been reported after FEF lesions alone. The impairment of visual fixation in darkness and the lack of impairment under conditions of dim illumination appear to reflect a specific role for the FEF in spatial orientation in the absence of visual landmarks. The FEF also appears to play a more critical role than STP in smooth pursuit. By contrast, STP and the FEF appear to work cooperatively with respect to the production of saccades. We suggest that cortical oculomotor control can flow either through the midbrain or through the FEF and that the FEF pathway is specifically involved in tasks with a discontiguity between the stimuli and the behavioral response while the midbrain pathways are preferentially involved in more stimulus-driven eye movements.

Neural substrates of sound localization

Recent behavioral experiments suggest that parallel pathways in the forebrain and midbrain are capable of mediating sound localization. Neurophysiological studies have advanced our understanding of how binaural and monaural localization cues contribute to the representations of auditory space within these pathways. Experience-dependent modifications of auditory spatial tuning in both the forebrain and midbrain pathways indicate that sensory input during development customizes an individual's neural processing of spatial information.

Parallel pathways mediating both sound localization and gaze control in the forebrain and midbrain of the barn owl

The hypothesis that sound localization and gaze control are mediated in parallel in the midbrain and forebrain was tested in the barn owl. The midbrain pathway for gaze control was interrupted by reversible inactivation (muscimol injection) or lesion of the optic tectum. Auditory input to the forebrain was disrupted by reversible inactivation or lesion of the primary thalamic auditory nucleus, nucleus ovoidalis (homolog of the medial geniculate nucleus). Barn owls were trained to orient their gaze toward auditory or visual stimuli presented from random locations in a darkened sound chamber. Auditory and visual test stimuli were brief so that the stimulus was over before the orienting response was completed. The accuracy and kinetics of the orienting responses were measured with a search coil attached to the head. Unilateral inactivation of the optic tectum had immediate and long-lasting effects on auditory orienting behavior. The owls failed to respond on a high percentage of trials when the auditory test stimulus was located on the side contralateral to the inactivated tectum. When they did respond, the response was usually (but not always) short of the target, and the latency of the response was abnormally long. When the auditory stimulus was located on the side ipsilateral to the inactivated tectum, responses were reliable and accurate, and the latency of responses was shorter than normal. In a tectally lesioned animal, response probability and latency to contralateral sounds returned to normal within 2 weeks, but the increase in response error (due to undershooting) persisted for at least 12 weeks. Despite abnormalities in the response, all of the owls were capable of localizing and orienting to contralateral auditory stimuli on some trials with the optic tectum inactivated or lesioned. This was not true for contralateral visual stimuli. Immediately following tectal inactivation, the owls exhibited complete neglect for visual stimuli located more than 20 degrees to the contralateral side (i.e., beyond the edge of the visual field of the ipsilateral eye). In the tectally lesioned animal, this neglect diminished with time. Unilateral inactivation of nucleus ovoidalis had different effects in three owls. Response error to contralateral sound sources increased for one owl and decreased for two; response error to ipsilateral sources did not change significantly for any. The probability of response to ipsilateral (but not contralateral) stimuli decreased for one owl. The latency of response to ipsilateral (but not contralateral) stimuli increased for one and decreased for another. All of the owls, however, routinely localized and oriented toward ipsilateral and contralateral auditory stimuli with nucleus ovoidalis inactivated.(ABSTRACT TRUNCATED AT 400 WORDS)

Saccade preparation inhibits reorienting to recently attended locations.

We measured manual reaction time in normal human subjects to confirm that an eccentric visual signal has a biphasic effect on covert attention and eye movements. First, it summons attention and biases a saccade toward the signal; a subsequent inhibition of return then slows responses to signals at that location. A temporal hemifield dominance for inhibition of return was shown; this finding converges with observations in neurologic patients to suggest that it is mediated by midbrain pathways. Endogenous orienting of attention, from a central arrow cue, did not activate inhibition of return, whereas endogenous saccade preparation did so as effectively as an exogenous signal, even when no saccade was made. Inhibition of return is activated by midbrain oculomotor pathways and may function as a location "tagging" mechanism to optimize efficiency of visual search.

Neural systems control of spatial orienting.

A peripheral visual cue in an empty field (1) often summons head or eyes, or both, (2) improves efficiency at the cued position while attention is directed to it, even without overt movements, and (3) reduces processing efficiency at the cued position once attention is withdrawn. We have studied the time course and the effects of mid-brain and cortical damage on these components of orienting. The facilitation arises from shifts in covert attention. In cases of mid-brain degeneration due to progressive supranuclear palsy, saccadic movements were abolished, while covert orienting still occurs. However, covert orienting was found to be delayed in directions in which eye movements were most affected, suggesting a role for mid-brain pathways in covert orienting. Parietal lesions can cause massive loss in detection contralateral to the lesion. This is especially true when attention has been directed to the opposite side. These findings relate aspects of covert orienting of attention to neural control systems.

Midbrain pathways for the initiation and maintenance of the nocturnal prolactin surge in pseudopregnant rats.

After stimulation of the uterine cervix of the rat, a nocturnal PRL surge that is responsible for pseudopregnancy is initiated and maintained daily. This study was designed to determine the midbrain pathways for the neural control of the initiation and maintenance of the nocturnal PRL surge in pseudopregnant rats. Cervical stimulation, applied in the evening of proestrus, initiated a nocturnal PRL surge in the early morning of estrus. Neural transections, when placed in the ventromedial or lateral part of the midbrain before cervical stimulation, completely suppressed the nocturnal surge, whereas sham transections or transections in the dorsal part of the midbrain did not eliminate the nocturnal surge. On the other hand, in rats that received sham transections in the evening on day 5 of pseudopregnancy previously induced by cervical stimulation, a nocturnal PRL surge was observed in the early morning on day 6. None of transections in the ventromedial, lateral, or dorsal part of the midbrain placed in the evening on day 5 of pseudopregnancy affected the nocturnal surge on day 6. These results suggest that the initiation of the nocturnal PRL surge by cervical stimulation requires the neural components that are contained in the ventromedial and lateral parts of the midbrain. In contrast, the maintenance of the nocturnal surge possibly occurs independent of neural afferents from the midbrain.

Hypothalamic and midbrain neural pathways involved in eating, drinking, irritability, aggression, and copulation in rats.

Hypothalamic and midbrain neural pathways involved in eating, drinking, irritability, aggression, and copulation in rats.

Sleep and other behavioural effects induced by acetylcholinic stimulation of basal temporal cortex and striate structures

Summary Hypogenic structures in the temporal lobe and basal ganglia were mapped out by the method of localized chemical stimulation which has recently disclosed a hypnogenic limbic midbrain pathway. Specially devised cannulae and electrodes were permanently implanted in the brain of cats, and a correlated study of the behavioural and electrographic effects was carried out. It was found that the application of minute crystals of acetylcholine successively induced the behavioural and electrographic manifestations of the two patterns of sleep, only when applied to certain anatomical structures including the prepyriform and periamygdaloid cortex, the olfactory tubercle, the anterior and posterior sylvian cortex, the entopeduncular nucleus, the globus pallidus, the putamen, and the caudate nucleus. Chemically induced sleep was readily conditioned to the external environment. In a few experiments, narcoleptic and cataplectic-like responses were elicited from the pyriform cortex. Cortically induced sleep was prevented by lesions involving either the medial forebrain bundle (MFB), or the n. ventralis anterior of the thalamus, or the n. reticularis gigantocellularis in the rostral medullary tegmentum. Lesions involving midbrain or pontine structures, including the n. reticularis pontis caudalis, were ineffective in interfering with acetylcholinic sleep of cortical origin. Anatomical connections between the hypnogenic pyriform cortex and the MFB were confirmed by neuronography. In addition to the sleep effects, a wide variety of autonomic and somatomotor responses, sometimes integrated as emotional behaviour or seizures, were obtained by acetylcholinic stimulation of other anatomical loci. Besides demonstrating cortical hypnogenic areas corresponding to the uncus and insula of the primate brain, the abovementioned results indicate the important participation of the MFB and of the bulbar reticular formation in cortically induced sleep. It is suggested that the clinical syndrome of narcolepsycataplexy may arise from parosysmal activity in the pyriform cortex.

The effects of morphine and pethidine on somatic evoked responses in the midbrain of the cat, and their relevance to analgesia

1. 1. In normal cats, morphine at 2 mg/kg and pethidine at 4 mg/kg, intravenously, conferred analgesia to ear-pinching with minimal side-effects. At 4–6 mg/kg, the side-effects of morphine were marked, and included hyperkinesia, abnormalities of gait, and escape behaviour. Side-effects were less prominent with pethidine up to 7 mg/kg. 2. 2. At low doses where side-effects are minimal, morphine and pethidine selectively depressed somatic evoked responses in peripheral areas of the midbrain, principally paralemniscal and ventral tegmental areas. At higher doses where side-effects predominate, responses in the medial midbrain pathways were also depressed. 3. 3. The anaesthetic agents nitrous oxide, ether and pentobarbital depressed responses with a pattern of selectivity different from that of the narcotic analgesics, since the medially-located pathways were preferentially affected. 4. 4. Pethidine differed from morphine in having little or no effect on deep tectal responses, and in a tendency to depressed ipsilateral responses selectively in the lateral midbrain. 5. 5. It is concluded that depression in peripheral midbrain areas is related to the analgesic action of morphine and pethidine, whereas depression of the medially-located pathways of the ascending reticular system involves effects on consciousness other than analgesia.