Response properties of neurons in inferior colliculi of mice made susceptible to audiogenic seizures by acoustic priming.

Mice not normally susceptible to audiogenic seizures can be rendered so by exposing them to a brief intense sound during a certain developmental period (acoustic priming). To determine the effects of priming on central auditory activity, single-unit extracellular recordings were obtained from the inferior colliculi of primed C57BL/6J mice. Response patterns were observed in primed mice that were not found in nonprimed mice of the same strain. These responses were characterized by prolonged discharges to clicks and/or afterdischarges to tones in 19 of 265 units studied. For the overall sample of units, absolute thresholds were consistently elevated, low-frequency responsiveness was diminished, and the proportion of units displaying response patterns that involve inhibitory influence was reduced (onset, off, inhibition, pauser, long-latency). The incidence and rates of spontaneous activity in primed mice did not differ significantly from those found in nonprimed mice. The data suggest that acoustic priming may increase behavioral responsiveness to intense sounds by disrupting the interplay of excitation and inhibition in the central auditory system.     

The influence of stimulus repetition on the acoustic startle response and on responses of inferior colliculus neurons of mice

The acoustic startle response (ASR) and discharges of single units in the inferior colliculus (IC) were evaluated as a function of the repetition rate and trial (stimulus 1–10 at each rate) of intense noise bursts in mice. The amplitude of the ASR was inversely proportional to both rate and trial. The mean number of discharges for the sample population of units of the central nucleus (ICC) and the external nucleus (ICX) were also inversely proportional to stimulus rate. However, only ICX units were inversely proportional to trial (i.e. as was the ASR). When response properties of individual units were examined, a variety of profiles was observed with regard to rate and trial sensitivity: units were either not sensitive to stimulus rate, inversely sensitive, directly sensitive, or complexly sensitive. Superimposed on these rate classifications were trial sensitivity, with some units being insensitive to trial, directly sensitive, or inversely sensitive. The incidence of response types differed in some respects between ICC and ICX and these differences were, in general, consistent with the mean responses of the neuronal populations.     

Distribution within the barn owl's inferior colliculus of neurons projecting to the optic tectum and thalamus

Behavioral studies in barn owls indicate that both the optic tectum (OT) and the auditory arcopallium (AAr) mediate sound localization through the presence of neurons that respond only when sound comes from a circumscribed direction in space. The early stages of the computations leading to these so-called space-specific neurons are shared in a common brainstem pathway, which then splits at the level of the inferior colliculus (IC) such that the last computational stage is thought to be duplicated. The study presented here addresses whether the space-specific neurons in OT and AAr are indeed partially independent of each other by using anatomical methods more precise than those used in previous studies. Specifically, projection neurons in IC were retrogradely labelled with injections of fluorescein- and rhodamine-conjugated dextran amines into OT and nucleus ovoidalis (OV), the thalamic nucleus leading to AAr. By labelling the OT-projecting and OV-projecting neurons in the same owl, it was confirmed that neurons in IC project to either OV or OT but not both. However, although a segregation was generally observed between the medially positioned OV-projecting neurons and the laterally positioned OT-projecting neurons, there was also a slight overlap between the two populations. Moreover, electrolytic lesions demarcating physiological tuning properties indicate that many OV-projecting neurons are within the area containing space-specific neurons. These results highlight the need for more detailed studies elucidating the microcircuitry and corresponding physiology of IC, such as have been done in the cortices of the mammalian cerebellum and cerebrum.     

The organization of neurons in the nucleus of the lateral lemniscus projecting to the superior and inferior colliculi in the rat

The topographic organization of neurons in the dorsal nucleus of the lateral lemniscus (DNLL) which project to the superior and inferior colliculi was studied using the retrograde horseradish peroxidase (HRP) and the fluorescent double labeling methods. Neurons projecting to the superior colliculus (SC) are situated in the rostral portion of the DNLL, whereas those to the inferior colliculus (IC) are found in the caudal area of this nucleus. These two portions are completely separated from each other and no neurons projecting to both the SC and the IC are observed. In the dorsolateral part of the rostral portion of the DNLL, neurons projecting to the ipsilateral SC are found, whereas neurons projecting to the contralateral SC are located in the central to medial part of the nucleus, but no neurons sending collateral axons to both sides of the SC were observed. Neurons located in the central part of the caudal area of the DNLL project to the ipsilateral IC and neurons in the lateral and medial parts project contralaterally to the IC. Some of the neurons in the caudal part of the DNLL have divergent axonal branching projecting to both sides of the IC. In the ventral nucleus of the lateral lemniscus, labeled neurons were observed only when the HRP was injected into the ipsilateral IC.     

Transneuronal transport in the vestibular and auditory systems of the squirrel monkey and the arctic ground squirrel. II. Auditory system

Transneuronal transport in the auditory system of the squirrel monkey and the arctic ground squirrel was studied after implantation of tritiated protein or glycoprotein precursors into the ampulla of a single semicircular duct. In both species, essentially the same pattern of transneuronal transport extended beyond the cochlear nuclei to the central nucleus of the inferior colliculus (CNIC), after survival periods ranging from 9 to 33 days. Animals displayed dense labeling over nearly all auditory receptors, nearly all portions of the spiral ganglion and throughout the cochlear nuclei (CN). Labeled fibers, mainly in the ventral acoustic stria, terminated over the ipsilateral lateral superior olive (LSO) and the lateral aspect of medial superior olive (MSO). Fibers continuing medially, decussated in an orderly manner, and terminated over the opposite medial nucleus of the trapezoid body (MNTB) and medial aspect of MSO. Labeled fibers projecting into the opposite lateral lemniscus (LL) terminated in the ventral nucleus of the lateral lemniscus (VNLL) and the CNIC. Fibers, but few terminals, were noted over the dorsal nucleus of the LL. The ipsilateral LL contained comparatively few labeled fibers, but sparse terminations occurred over portions of VNLL and CNIC. No transport of [3H]precursors was noted in the peripheral nuclei of the inferior colliculus or in the medial geneculate body on either side. Massive transport via the contralateral LL and the profuse terminals in the opposite CNIC suggested transneuronal transport via secondary and higher order auditory fibers. Although the largest number of fibers in the contralateral LL probably arose from the cochlear nuclei, higher order fibers also may have arisen from the ipsilateral LSO and the contralateral MSO and VNLL. Small numbers of fibers in both species descended from the region of the superior olivary complex (SOC) ventral to the facial motor nucleus. In the ground squirrel, scant auditory projections were traced into the opposite cochlear nuclei. Tritiated precursors in the endolymph passed most readily from labyrinth to cochlea, and transneuronal transport was more extensive in the auditory pathways than in the vestibular system at comparable times. Centrally transported [3H]fucose was cleared more promptly than [3H]proline in monkeys.     

Diencephalic modulation of activities of raphe-spinal neurons in the cat

The modulatory effects of diencephalic stimulation on the activities of raphe-spinal neurons were studied extracellularly in cats. Among 240 raphe neurons recorded, 57 neurons were activated antidromically by stimulation of the cervical dorsolateral funiculus. These raphe-spinal neurons were found in the caudal raphe nuclei, i.e., the raphe magnus (43 neurons), raphe obscurus (11), raphe pallidus (2), and raphe pontis (1). All of them responded to innocuous and/or noxious peripheral mechanical stimuli with a broad receptive field. The activities of the majority of these neurons were facilitated by trains of pulse stimulation of the rostral periaqueductal gray and the thalamic relay nucleus but not of the thalamic center median nucleus. The facilitation of firing persisted for more than 3 min after the cessation of train pulse stimulation when the stimulation was applied at 20 Hz for 5 to 30 s. This facilitation was not affected by decortication of the sensorimotor area bilaterally. The facilitatory response to periaqueductal gray stimulation was markedly suppressed by systemic administration of naloxone. On the other hand, that of the thalamic relay nucleus stimulation was found to be unaffected. Based on these findings, the mechanisms of pain relief by stimulation of the rostral periaqueductal gray and thalamic relay nucleus reported in human intractable pain appear to relate, at least partly, to the activation of raphe-spinal neurons. However, the paths to raphe-spinal neurons of stimuli from the periaqueductal gray and the thalamic relay nucleus are thought to be independent from each other based on the different effects of naloxone.     

Prenatal IV nicotine exposure produces a sex difference in sensorimotor gating of the auditory startle reflex in adult rats

Maternal smoking during pregnancy is associated with auditory processing deficits in children; these effects have been confirmed with animal models of continuous high-dose prenatal nicotine exposure. The present experiments utilized a novel, low-dose, intermittent, intravenous (IV) gestational nicotine exposure model to investigate potential deficits on the preattentive process of sensorimotor gating, as indexed by prepulse inhibition (PPI), in preweanling and adult rat offspring. Pregnant dams received bolus IV injections of nicotine (0.05 mg/kg/injection) 3×/day on gestational days 8-21. Auditory and tactile stimulus modalities were probed with tone and air puff prepulse stimuli, respectively. These prepulse stimuli preceded a 100 dB(A) startle tone by six different interstimulus intervals (ISIs; 0, 8, 40, 80, 120, 4000 ms) to define a curve of response inhibition. The magnitude of PPI increased with age, from 59 to 81% inhibition. Preweanlings (PNDs 14 and 18) and adults (PND 75) gestationally exposed to nicotine exhibited altered startle responding relative to controls, but the nature of the deficit became more localized at later ages. The entire curve of response inhibition in preweanlings exposed to prenatal nicotine (PND 14) was shifted up relative to controls, and notably, did not interact with prepulse stimulus modality, suggesting a generalized increased sensorimotor responsiveness as a function of prenatal nicotine. At PND 18, a shift in the response curve across all ISIs was again noted, but varied as a function of prepulse stimulus modality; the increased sensorimotor responsiveness was specific to the auditory, but not tactile, sensory modality. In adulthood, male and female animals prenatally exposed to nicotine were differentially sensitive to modulation by the ISIs, relative to control male and female animals. Specifically, despite robust PPI, adult females exposed to gestational nicotine were relatively insensitive to changes in ISI from 8 to 120 ms; in contrast, the robust PPI of nicotine-exposed males demonstrated a clear focal point of inhibition at 40 ms. These findings indicate that a low, daily dosing of IV prenatal nicotine produces long-lasting alterations in auditory PPI. An important implication of this research is that “chipping” with smoked-tobacco products during pregnancy may produce enduring changes in sensorimotor processing.     

Electroacupuncture induces c-Fos expression in the rostral ventrolateral medulla and periaqueductal gray in cats: relation to opioid containing neurons

Our previous studies have shown that electroacupuncture (EA) at the Neiguan-Jianshi (P5-P6) acupoints inhibits sympathetic outflow and attenuates excitatory visceral cardiovascular reflexes through enkephalin- or beta-endorphin-related opioid receptors in the rostral ventrolateral medulla (rVLM). It is not known whether EA at these acupoints activates neurons containing enkephalin or beta-endorphin in the rVLM as well as in the periaqueductal gray (PAG) that are involved in EA-mediated central neural regulation of sympathetic activity. The present study evaluated activated neurons in the rVLM and PAG by detecting c-Fos immunoreactivity, and identified the relationship between c-Fos nuclei and neuronal structures containing enkephalin or beta-endorphin in these regions. To enhance the detection of cell bodies containing enkephalin or beta-endorphin, colchicine (90-100 microg/kg) was injected into the subarachnoid space in anesthetized cats 28-30 h prior to EA or the sham-operated control for EA. Following bilateral barodenervation and cervical vagotomy, EA (1-4 mA, 2 Hz, 0.5 ms) was performed at the P5-P6 acupoints (overlying median nerve; n=7) for 30 min. Identical procedures, with the exception of electrical stimulation, were carried out in five control animals. EA decreased blood pressure (BP) in four of seven cats (5-15 mm Hg) while the sham procedure for EA produced no responses. Perikarya containing enkephalin were found in the rVLM and rarely in the PAG, while no cell bodies labeled with beta-endorphin were identified in either region. Compared to animals in the control group, more c-Fos immunoreactivity, located principally in close proximity to fibers containing enkephalin or beta-endorphin, was observed in the rVLM and ventrolateral PAG (vlPAG) in EA-treated cats. Moreover, neurons double-labeled with c-Fos and enkephalin in the rVLM were significantly increased in cats following EA stimulation (P<0.05). These data indicate that EA at the P5-P6 acupoints activates neurons in the rVLM and vlPAG. These activated neurons contain enkephalin in the rVLM, and most likely interact with nerve fibers containing enkephalin or beta-endorphin in both the rVLM and vlPAG. The results from this study provide the first anatomical evidence showing that EA at the P5-P6 acupoints has the potential to influence neuronal structures (perikarya, axons and/or dendrites) containing enkephalin or beta-endorphin in specific regions of the brain stem. These neurons likely form the substrate for EA's influence on sympathoexcitatory cardiovascular reflexes.     

Role of the bed nucleus of the stria terminalis in the control of ventral tegmental area dopamine neurons

Projections from neurons of the bed nucleus of the stria terminalis (BST) to the ventral tegmental area (VTA) are crucial to behaviors related to reward and motivation. Over the past few years, we have undertaken a series of studies to understand: 1) how excitatory inputs regulate in vivo excitable properties of BST neurons, and 2) how BST inputs in turn modulate neuronal activity of dopamine neurons in VTA. Using in vivo extracellular recording techniques in anesthetized rats and tract-tracing approaches, we have demonstrated that inputs from the infralimbic cortex and the ventral subiculum exert a strong excitatory influence on BST neurons projecting to the VTA. Thus, the BST is uniquely positioned to receive emotional and learning-associated informations and to integrate these into the reward/motivation circuitry. We will discuss how changes in the activity of BST neurons projecting to the VTA could participate in the development or exacerbation of psychiatric conditions such as drug addiction.     

Electrical stimulation of the cochlear nerve in rats: analysis of c-Fos expression in auditory brainstem nuclei

We investigated functional activation of central auditory brainstem nuclei in response to direct electrical stimulation of the cochlear nerve using c-Fos immunoreactivity as a marker for functional mapping. The cochlear nerve was stimulated in the cerebellopontine angle of Lewis rats applying biphasic electrical pulses (120-250 muA, 5 Hz) for 30 min. In a control group, bilateral cochlectomy was performed in order to assess the basal expression of c-Fos in the auditory brainstem nuclei. The completeness of cochlear ablations and the response of auditory brainstem nuclei to electrical stimulation were electrophysiologically verified. C-Fos immunohistochemistry was performed using the free floating method. In anaesthetized animals with unilateral electrical stimulation of the cochlear nerve, increased expression of c-Fos was detected in the ipsilateral ventral cochlear nucleus (VCN), in the dorsal cochlear nucleus bilaterally (DCN), in the ipsilateral lateral superior olive (LSO) and in the contralateral inferior colliculus (IC). A bilateral slight increase of c-Fos expression in all subdivisions of the lateral lemniscus (LL) did not reach statistical significance. Contralateral inhibition of the nuclei of the trapezoid body (TB) was observed. Our data show that unilateral electrical stimulation of the cochlear nerve leads to increased expression of c-Fos in most auditory brainstem nuclei, similar to monaural auditory stimulation. They also confirm previous studies suggesting inhibitory connections between the cochlear nuclei. C-Fos immunoreactivity mapping is an efficient tool to detect functional changes following direct electrical stimulation of the cochlear nerve on the cellular level. This could be particularly helpful in studies of differential activation of the central auditory system by experimental cochlear and brainstem implants.     

Conditioned place aversion organized in the dorsal periaqueductal gray recruits the laterodorsal nucleus of the thalamus and the basolateral amygdala

The amygdala-ventral periaqueductal gray circuit is crucial for the expression of contextual conditioned fear. However, little is known about the neural circuits activated when the stimulation of the dorsal periaqueductal gray (dPAG) is used as unconditioned stimulus (US) in conditioned fear paradigms. The present paper examines the Fos-protein distribution in the brain of rats submitted to a conditioned place aversion (CPA) paradigm using the dPAG chemical stimulation with semicarbazide (SMC), an inhibitor of the GABA synthesizing enzyme, as US and the quadrant of an arena where the drug was injected as the paired neutral stimulus. Our results show that CPA associated with SMC injections caused a significant Fos labeling in the laterodorsal nucleus of the thalamus (LD), basolateral nucleus of amygdala (BLA) and in the dorsomedial PAG (dmPAG). This pattern of brain activation is clearly different from the neural substrates of the classical fear conditioning reported in the literature. Moreover, this paper shows that CPA with the use of chemical stimulation of the dPAG could be used as an experimental model of panic disorder with agoraphobia in the extent that panic attacks repeatedly associated with specific contexts may turn in this condition in the clinics. This condition activates the BLA probably through the LD. Besides, it indicates that the dPAG can be the link between amygdala and the brainstem motor regions that controls CPA when dPAG stimulation is used as US instead of footshocks. From this evidence we suggest that a loop dPAG-LD-BLA-dPAG is activated during the panic disorder with agoraphobia.     

Evidence for in vivo thermosensitivity of serotonergic neurons in the rat dorsal raphe nucleus and raphe pallidus nucleus implicated in thermoregulatory cooling

The ability to sense and respond appropriately to increases in ambient and body temperatures is critical for the survival of all animals. Although evidence suggests that brain serotonergic systems play a role in thermoregulation, including thermoregulatory cooling, evidence for activation of brainstem serotonergic neurons in vivo, in unanesthetized animals, during heat exposure is lacking. In this experiment we tested the hypothesis that populations of serotonergic neurons in the midbrain and medullary raphe complex are activated following exposure to warm ambient temperature. Rats were exposed to an incubation chamber at either warm ambient temperature (37 °C) or room temperature (RT; 23 °C) for 105 min. Brains then were removed and processed for immunohistochemical detection of the protein product of the immediate-early gene c-fos (as a marker of neuronal activation) and tryptophan hydroxylase (as a marker of serotonergic neurons). Exposure to warm ambient temperature increased body temperature and c-Fos expression in topographically organized populations of serotonergic neurons in the dorsal raphe nucleus. Activation of the dorsal raphe nucleus serotonergic system was positively correlated with body temperature following exposure to the incubation chamber. In the medulla, exposure to warm ambient temperature, compared with exposure to RT, decreased c-Fos expression in serotonergic neurons in the raphe pallidus nucleus and in non-serotonergic cells in the rostral ventrolateral medulla. Together, these results provide evidence for multiple but anatomically discrete thermosensitive serotonergic systems that may have implications for the regulation of body temperature, as well as, via projections to forebrain targets, cognitive and affective functions.     

Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat

We have analyzed at high resolution the neuroanatomical connections of the juxtaparaventricular region of the lateral hypothalamic area (LHAjp); as a control and in comparison to this, we also performed a preliminary analysis of a nearby LHA region that is dorsal to the fornix, namely the LHA suprafornical region (LHAs). The connections of these LHA regions were revealed with a coinjection tract-tracing technique involving a retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracer. The LHAjp and LHAs together connect with almost every major division of the cerebrum and cerebrospinal trunk, but their connection profiles are markedly different and distinct. In simple terms, the connections of the LHAjp indicate a possible primary role in the modulation of defensive behavior; for the LHAs, a role in the modulation of ingestive behavior is suggested. However, the relation of the LHAjp and LHAs to potential modulation of these behaviors, as indicated by their neuroanatomical connections, appears to be highly integrative as it includes each of the major functional divisions of the nervous system that together determine behavior, i.e., cognitive, state, sensory, and motor. Furthermore, although a primary role is indicated for each region with respect to a particular mode of behavior, intermode modulation of behavior is also indicated. In summary, the extrinsic connections of the LHAjp and LHAs (so far as we have described them) suggest that these regions have a profoundly integrative role in which they may participate in the orchestrated modulation of elaborate behavioral repertoires.     

The Retinohypothalamic tract: Comparison of axonal projection patterns from four major targets

The retinohypothalamic tract is one component of the optic nerve that transmits information about environmental luminance levels through medial and lateral branches to four major terminal fields in the hypothalamus. The spatial distribution and organization of axonal projections from each of these four terminal fields were analyzed and compared systematically with the anterograde pathway tracer PHAL in rats where the terminal fields had been labeled with intravitreal injections of a different anterograde pathway tracer, CTb. First, the well-known projections of two medial retinohypothalamic tract targets (the ventrolateral suprachiasmatic nucleus and perisuprachiasmatic region) were confirmed and extended. They share qualitatively similar projections to a well-known set of brain regions thought to control circadian rhythms. Second, the projections of a third medial tract target, the ventromedial part of the anterior hypothalamic nucleus, were analyzed for the first time and shown to resemble qualitatively those from the suprachiasmatic nucleus and perisuprachiasmatic region. And third, projections from the major lateral retinohypothalamic tract target were analyzed for the first time and shown to be quite different from those associated with medial tract targets. This target is a distinct core part of the ventral zone of the anterior group of the lateral hypothalamic area that lies just dorsal to the caudal two-thirds of the supraoptic nucleus. Its axonal projections are to neural networks that control a range of specific goal-oriented behaviors (especially drinking, reproductive, and defensive) along with adaptively appropriate and complementary visceral responses and adjustments to behavioral state.     

Cytoarchitecture and thalamic afferents of the sylvian and composite posterior gyri of the canine temporal cortex

The composite posterior and sylvian gyri of the canine temporal cortex show cytoarchitectonic features of poorly differentiated isocortex. Quantitative evaluation of connections examined with retrogradely transported fluorescent tracers indicated that both gyri received strong thalamic projections from the medial geniculate body (MG) and the lateromedial-suprageniculate (LM-Sg) complex, and a weaker projection from the posterior (Po) nuclei. On the basis of the connectivity patterns and cytoarchitectonic features we distinguished the anterior (CPa) and posterior (CPp) areas in posterior composite gyrus and the anterior (SA), dorsal (SD) and posterior (SP) sylvian areas. Afferents from individual thalamic nuclei were focused in distinct areas, forming dominant projections, and diminished gradually in the adjacent areas as non-dominant projections. The most prominent MG projection arose from the dorsal caudal (MGdc) nucleus. Its ventral subdivision sent a dominant projection into the SP and CPa, whereas the dorsal MGdc subdivision was connected with the SA, SD and CPp areas. The most substantial connections from the LM-Sg complex were directed to areas SA, SD and CPp, with weak connections to areas CPa and SP. A gradient of density of LM-Sg afferents was distributed in the opposite direction to that sent from the MGdc. The origin of the CPa and SP afferents in the ventral MGdc, like connections reaching the posterior ectosylvian cortex, suggest that these areas are related to processing of auditory information. In contrast, areas SA and CPp, receive dominant projections from the polymodal LM-Sg, and therefore may constitute successive steps in a hierarchy of cortical areas.     

Selective participation of the bed nucleus of the stria terminalis and CRF in sustained anxiety-like versus phasic fear-like responses

The medial division of the central nucleus of the amygdala (CeA_M) and the lateral division of the bed nucleus of the stria terminalis (BNST_L) are closely related. Both receive projections from the basolateral amygdala (BLA) and both project to brain areas that mediate fear-influenced behaviors. In contrast to CeA_M however, initial attempts to implicate the BNST in conditioned fear responses were largely unsuccessful. More recent studies have shown that the BNST does participate in some types of anxiety and stress responses. Here, we review evidence suggesting that the CeA_M and BNST_L are functionally complementary, with CeA_M mediating short- but not long-duration threat responses (i.e., phasic fear) and BNST_L mediating long- but not short-duration responses (sustained fear or ‘anxiety’). We also review findings implicating the stress-related peptide corticotropin-releasing factor (CRF) in sustained but not phasic threat responses, and attempt to integrate these findings into a neural circuit model which accounts for these and related observations.     

Projections of the zona incerta in the cat, with stimulation controls.

In eight cats single electrolytic lesions were placed in the zona incerta, and resultant fiber degeneration studies were made. In seven additional cats, stimulating electrodes were chronically implanted bilaterally into the zona incerta, H₂ (lenticular fasciculus), or H (prerubral) fields of Forel. The animals were placed in a two-compartment shuttle box, and a routinely established procedure of subthalamic stimulation was instituted. When the sensory (nociceptive) or motor manifestations and reactions were established, small lesions were made through both poles of the electrodes. The brains were studied by silver techniques for degenerating axons and terminals. Findings in the latter group of animals with physiologic substrates, compared to those in the first group, indicated that the zona incerta contains at least two major physiologic-anatomic components with differential fiber projections. The first component is a medial zona incerta proper or caudalis, paleospinothalamic, nociceptive-conducting system which causes typical escape responses. Its unequivocal projections are to the nucleus of the H₁ field, posterior and dorsal hypothalamus, part of the intralaminar system, ventromedial and ventralis anterior nuclei, nucleus reuniens, reticular nucleus, pulvinar, posterior nucleus, central gray, red nucleus, and the central tegmental tract. The second constitutent concerns pyramidal-extrapyramidal motor type responses that arise with avoidance reactions from other portions of the zona incerta. In these cases there is heavy projection to the caudate, entopenduncular, globus pallidus, and putamen nuclei. In contrast, degeneration from the nociceptive part of the zona incerta or H₂ and H fields to these nuclei is minimal.