Ventral Zona Incerta Research Articles

Ventral zona incerta parvalbumin neurons modulate sensory-induced and stress-induced self-grooming via input-dependent mechanisms in mice

Self-grooming is an innate stereotyped behavior influenced by sense and emotion. It is considered an important characteristic in various disease models. However, the neural circuit mechanism underlying sensory-induced and emotion-driven self-grooming remains unclear. We found that the ventral zona incerta (Ziv) was activated during spontaneous self-grooming (SG), corn oil-induced sensory self-grooming (OG), and tail suspension-induced stress self-grooming (TG). Optogenetic excitation of Ziv parvalbumin (PV) neurons increased the duration of SG. Conversely, optogenetic inhibition of ZivPV neurons significantly reduced self-grooming in all three models. Furthermore, glutamatergic inputs from the primary sensory cortex activated the Ziv and contributed to OG. Activation of GABAergic inputs from the central amygdala to the Ziv increased SG, OG, and TG, potentially through local negative regulation of the Ziv. These findings suggest that the Ziv may play a crucial role in processing sensory and emotional information related to self-grooming, making it a potential target for regulating stereotyped behavior.

Unilateral optogenetic stimulation of Lhx6 neurons in the zona incerta increases REM sleep.

To determine how a waking brain falls asleep researchers have monitored and manipulated activity of neurons and glia in various brain regions. While imaging Gamma-Aminobutyric Acid (GABA) neurons in the zona incerta (ZI) we found a subgroup that anticipates onset of NREM sleep (Blanco-Centurion C, Luo S, Vidal-Ortiz A, Swank C, Shiromani PJ. Activity of a subset of vesicular GABA-transporter neurons in the ventral ZI anticipates sleep onset. Sleep. 2021;44(6):zsaa268. doi:10.1093/sleep/zsaa268.). To differentiate the GABA subtype we now image and optogenetically manipulate the ZI neurons containing the transcription factor, Lhx6. In the first study, Lhx6-cre mice (n = 5; female = 4) were given rAAV-DJ-EF1a-DIO-GCaMP6M into the ZI (isofluorane anesthesia), a GRIN lens implanted, and 21days later sleep and fluorescence in individual Lhx6 neurons were recorded for 4 hours. Calcium fluorescence was detected in 132 neurons. 45.5% of the Lhx6 neurons were REM-max; 30.3% were wake-max; 11.4% were wake + REM max; 9% were NREM-max; and 3.8% had no change. The NREM-max group of neurons fluoresced 30 seconds ahead of sleep onset. The second study tested the effects of unilateral optogenetic stimulation of the ZI Lhx6 neurons (n = 14 mice) (AAV5-Syn-FLEX-rc[ChrimsonR-tdTomato]. Stimulation at 1 and 5 Hz (1 minute on- 4 minutes off) significantly increased percent REM sleep during the 4 hours stimulation period (last half of day cycle). The typical experimental approach is to stimulate neurons in both hemispheres, but here we found that low-frequency stimulation of ZI Lhx6 neurons in one hemisphere is sufficient to shift states of consciousness. Detailed mapping combined with mechanistic testing is necessary to identify local nodes that can shift the brain between wake-sleep states.

Projections from LIM homeobox 6 (Lhx6) + zona incerta neurons to the cholinergic or monoaminergic nuclei of the rat.

A recent report suggested that LIM homeobox 6 (Lhx6) + GABA-releasing neurons of the ventral zona incerta (VZI) promote sleep, particularly paradoxical sleep (PS). While their potential involvement in sleep still needs to be firmly confirmed, little is known about their specific input/output connections with widespread brain regions, including those involved in sleep. Thus, the present study was designed to examine whether Lhx6-expressing neurons (in parallel to intermingled MCH-expressing ones) may send efferent projections to cholinergic and/or monoaminergic nuclei from basal forebrain (BF) to brainstem (BS). Based on the present observations, the proportions of Lhx6+ neuronal projection to the BF and BS cholinergic nuclei over the total number of Lhx6+ VZI cells were approximately 5.9% and 6.9%, respectively. Likewise, the proportions of Lhx6+ neuronal projection to the dorsal raphe and locus coeruleus over the total number of Lhx6+ VZI cells were about 4.3% and 3.9%, respectively. In addition, Lhx6+ cells projecting to the cholinergic or monoaminergic nuclei were scattered along the entire dorsal-to-ventral extent of the VZI. Based on the present as well as our previous observations, it is suggested that Lhx6+ VZI neurons might play an important role in the regulation of PS, partly via the neural network involving the cholinergic as well as monoaminergic nuclei of the rat.

Microglial Engulfment of Spines in the Ventral Zona Incerta Regulates Anxiety-Like Behaviors in a Mouse Model of Acute Pain.

Although activation of microglial cells is critical in developing brain disorders, their role in anxiety-like behaviors in pain is still vague. This study indicates that alteration of microglia’s neuronal spine engulfment capacity in ventral zona incerta (ZIV) leads to significant pain and anxiety-like behaviors in mice 1-day post-injection of Complete Freud’s Adjuvant (CFA1D). Performing whole-cell patch-clamp recordings in GABAergic neurons in the ZIV (ZIVGABA) in brain slices, we observed decreased activity in ZIvGABA and reduced frequency of the miniature excitatory postsynaptic currents (mEPSCs) in ZIVGABA of CFA1D mice compared with the saline1D mice. Besides, chemogenetic activation of ZIVGABA significantly relieved pain and anxiety-like behaviors in CFA1D mice. Conversely, in naïve mice, chemogenetic inhibition of ZIVGABA induced pain and anxiety-like behaviors. Interestingly, we found changes in the density and morphology of ZIVMicroglia and increased microglial engulfment of spines in ZIV of CFA1D mice. Furthermore, pain sensitization and anxiety-like behaviors were reversed when the ZIVMicroglia of CFA1D-treated mice were chemically inhibited by intra-ZIV minocycline injection, accompanied by the recovery of decreased ZIVGABA excitability. Conclusively, our results provide novel insights that dysregulation of microglial engulfment capacity encodes maladaptation of ZIVGABA, thus promoting the development of anxiety-like behaviors in acute pain.

LIM homeobox 6 (Lhx6)+ neurons in the ventral zona incerta project to the core portion of the lateral supramammillary nucleus in the rat

There was a recent report suggesting that LIM homeobox 6 (Lhx6)+ GABA-releasing neurons of the ventral zona incerta (ZI) promote sleep. We demonstrated in the previous study that Lhx6+ ZI neurons are activated during paradoxical sleep (PS) hypersomnia which was induced by 48-hour PS deprivation, implying their roles in the control of PS like melanin-concentrating hormone (MCH) cells. Since the core portion of the lateral supramammillary nucleus (SUMl) is the major hypothalamic area activating the dentate gyrus as well as other limbic cortices during PS, we examined in the present study whether Lhx6+ ZI cells provide efferent projections to the SUMl, using the retrograde-tracing method. The majority of Lhx6+ neurons projecting to the SUMl occupied the ventral border (or ventral one-third) of the ventral ZI. Based on the quantitative analysis, the mean number of retrogradely-labeled Lhx6+ neurons was comparable to that of retrogradely-labeled MCH cells in the ZI. However, the total (i.e., single- plus double-labeled) number of Lhx6+ cells was approximately three times larger than that of MCH cells in the ZI. Thus, the proportion (about 7.8%) of retrogradely-labeled Lhx6+ neurons over the total Lhx6+ cells was approximately one-third of the percentage (about 20.9%) of retrogradely-labeled MCH neurons over the total MCH cells. On the other hand, a combination of retrogradely-labeled, Lhx6 and MCH cells occupied approximately 43.7% of the total retrogradely-labeled neurons in the ventral ZI. The present observations suggested that Lhx6+ neurons in the ventral ZI might play an important role in the regulation of PS, partly via the neural network involving the SUMl.

Incerta-thalamic Circuit Controls Nocifensive Behavior via Cannabinoid Type 1 Receptors

Pain is a source of substantial discomfort. Abnormal activity in both the zona incerta (ZI) and posterior complex of the thalamus (Po) are implicated in neuropathic pain, but their exact roles remain unclear. In particular, the precise cell types and molecular mechanisms of the ZI-Po circuit that regulate nociception are largely uncharacterized. Here, we found that parvalbumin (PV)-positive neuronal projections from the ventral ZI (ZIv) to the Po (ZIv-Po) are critical for promoting nocifensive behaviors, whereas selectively inhibiting ZIv-Po activity reduces nocifensive withdrawal responses. Furthermore, cannabinoid type 1 receptors (CB1Rs) are expressed specifically at ZIv-Po axon terminals in this circuit, and cannabinoids attenuate nocifensive responses through presynaptic inhibition. Selective inhibition of the ZIv-Po circuit or administration of cannabinoids into the Po are sufficient to ameliorate pathological pain. These findings identify the critical role of the ZIv-Po circuit and its modulation by endocannabinoids in controlling nocifensive behaviors.

Targeted recombination in active populations as a new mouse genetic model to study sleep-active neuronal populations: Demonstration that Lhx6+ neurons in the ventral zona incerta are activated during paradoxical sleep hypersomnia.

The cFos immunostaining allowed the identification of multiple populations of neurons involved in the generation of paradoxical sleep. We adopted the transgenic (targeted recombination in active populations) mouse model, which following injection of tamoxifen, allows expression of Cre-dependent reporter constructs (i.e., mCherry) in neurons expressing cFos during waking or paradoxical sleep hypersomnia following automatic paradoxical sleep deprivation. Three groups of mice were subjected to two periods of waking, one period of waking and one of paradoxical sleep hypersomnia, or two periods of paradoxical sleep hypersomnia. A high percentage of double-labelled neurons was observed in the lateral hypothalamic area and zona incerta of two periods of waking and two periods of paradoxical sleep hypersomnia in mice, but not in those of one period of waking and one of paradoxical sleep hypersomnia in animals. Melanin-concentrating hormone neurons in the lateral hypothalamic area and Lhx6+ cells in the zona incerta constituted 5.7±1.5% and 8.8±2.3% of all mCherry+ cells and 20.6±4.8% and 24.6±5.9% of all cFos+ neurons in two periods of paradoxical sleep hypersomnia in animals. In addition, melanin-concentrating hormone cells as well as Lhx6+ neurons rarely expressed mCherry (or cFos) in the waking condition, in contrast to orexin neurons, which constituted approximately 30% of mCherry+ and cFos+ neurons. Our results validate the TRAP methodology and open the way to use it for identifying the neurons activated during waking and paradoxical sleep hypersomnia. Furthermore, they indicate for the first time that Lhx6+ neurons in the zona incerta, like melanin-concentrating hormone cells in the lateral hypothalamic area, are activated during paradoxical sleep hypersomnia but not during waking. These results indicate that Lhx6+ neurons might play a role in the control of paradoxical sleep, like the melanin-concentrating hormone cells.

Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep.

Multiple populations of wake-promoting neurons have been characterized in mammals, but few sleep-promoting neurons have been identified. Wake-promoting cell types include hypocretin and GABA (γ-aminobutyric-acid)-releasing neurons of the lateral hypothalamus, which promote the transition to wakefulness from non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Here we show that a subset of GABAergic neurons in the mouse ventral zona incerta, which express the LIM homeodomain factor Lhx6 and are activated by sleep pressure, both directly inhibit wake-active hypocretin and GABAergic cells in the lateral hypothalamus and receive inputs from multiple sleep-wake-regulating neurons. Conditional deletion of Lhx6 from the developing diencephalon leads to decreases in both NREM and REM sleep. Furthermore, selective activation and inhibition of Lhx6-positive neurons in the ventral zona incerta bidirectionally regulate sleep time in adult mice, in part through hypocretin-dependent mechanisms. These studies identify a GABAergic subpopulation of neurons in the ventral zona incerta that promote sleep.

Vibrissa Self-Motion and Touch Are Reliably Encoded along the Same Somatosensory Pathway from Brainstem through Thalamus.

Active sensing involves the fusion of internally generated motor events with external sensation. For rodents, active somatosensation includes scanning the immediate environment with the mystacial vibrissae. In doing so, the vibrissae may touch an object at any angle in the whisk cycle. The representation of touch and vibrissa self-motion may in principle be encoded along separate pathways, or share a single pathway, from the periphery to cortex. Past studies established that the spike rates in neurons along the lemniscal pathway from receptors to cortex, which includes the principal trigeminal and ventral-posterior-medial thalamic nuclei, are substantially modulated by touch. In contrast, spike rates along the paralemniscal pathway, which includes the rostral spinal trigeminal interpolaris, posteromedial thalamic, and ventral zona incerta nuclei, are only weakly modulated by touch. Here we find that neurons along the lemniscal pathway robustly encode rhythmic whisking on a cycle-by-cycle basis, while encoding along the paralemniscal pathway is relatively poor. Thus, the representations of both touch and self-motion share one pathway. In fact, some individual neurons carry both signals, so that upstream neurons with a supralinear gain function could, in principle, demodulate these signals to recover the known decoding of touch as a function of vibrissa position in the whisk cycle.

Projections of somatosensory cortex and frontal eye fields onto incertotectal neurons in the cat

The goal of this study was to determine whether the input-output characteristics of the zona incerta (ZI) are appropriate for it to serve as a conduit for cortical control over saccade-related activity in the superior colliculus. The study utilized the neuronal tracers wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and biotinylated dextran amine (BDA) in the cat. Injections of WGA-HRP into primary somatosensory cortex (SI) revealed sparse, widespread nontopographic projections throughout ZI. In addition, region-specific areas of more intense termination were present in ventral ZI, although strict topography was not observed. In comparison, the frontal eye fields (FEF) also projected sparsely throughout ZI, but terminated more heavily, medially, along the border between the two sublaminae. Furthermore, retrogradely labeled incertocortical neurons were observed in both experiments. The relationship of these two cortical projections to incertotectal cells was also directly examined by retrogradely labeling incertotectal cells with WGA-HRP in animals that had also received cortical BDA injections. Labeled axonal arbors from both SI and FEF had thin, sparsely branched axons with numerous en passant boutons. They formed numerous close associations with the somata and dendrites of WGA-HRP-labeled incertotectal cells. In summary, these results indicate that both sensory and motor cortical inputs to ZI display similar morphologies and distributions. In addition, both display close associations with incertotectal cells, suggesting direct synaptic contact. From these data, we conclude that inputs from somatosensory and FEF cortex both play a role in controlling gaze-related activity in the superior colliculus by way of the inhibitory incertotectal projection.

Projections of the suprachiasmatic nuclei, subparaventricular zone and retrochiasmatic area in the golden hamster

The patterns of projections from the hamster suprachiasmatic nucleus, retrochiasmatic area and subparaventricular hypothalamic zone were examined using anterograde tracing with the plant lectin, Phaseolus vulgaris leucoagglutinin. Suprachiasmatic nucleus efferents comprise four major fiber groups: (i) an anterior projection to the ventral lateral septum, the bed nucleus of the stria terminalis and anterior paraventricular thalmus. (ii) a periventricular hypothalamic projection extending from the preoptic region to the premammillary area. (iii) a lateral thalamic projection to the intergeniculate leaflet and ventral lateral geniculate. (iv) a posterior projection to the posterior paraventricular thalamus, precommissural nucleus and olivary pretectal nucleus. The retrochiasmatic area showed a similar projection pattern with several major exceptions. There are projections to endopiriform cortex, fundus striati, ventral pallidum, horizontal limb of the nucleus of the diagonal band and three separate routes to the amygdala. There are also projections laterally with fibers of the supraoptic commissures, which enter the superior thalamic radiation and innervate the caudal dorsomedial thalamic nuclei. Other fibers traveling with the commissures terminate in the ventral zona incerta. The subparaventricular zone projects to most targets of the suprachiasmatic nucleus, but not to the intergeniculate leaflet. There is a substantial input to both the subparaventricular zone and retrochiasmatic area from the suprachiasmatic nucleus, but little apparent reciprocity. There is extensive overlap of suprachiasmatic nuclei and retrochiasmatic efferents, and between retrochiasmatic and known medial amygdaloid efferents. The anatomical information is discussed in the context of circadian rhythm regulation, photoperiodism and chemosensory pathways controlling male hamster reproductive behavior.

The sites of origin of α-melanocyte-stimulating hormone-containing axonal components in the lateral area of the midbrain periaqueductal gray of the rat

The sites of origin of alpha-melanocyte-stimulating hormone (alpha-MSH)-containing axonal components in the lateral area of the midbrain periaqueductal gray (PAG) were studied in the rat by the retrograde tracing method of horseradish peroxidase, combined with the immunocytochemical technique. The results indicated that alpha-MSH-containing axonal components in the PAG arose not only from the arcuate nucleus of the hypothalamus but also from the ventral zona incerta, the periventricular, perifornical and lateral hypothalamic regions.

Anticonvulsant role of nigrotectal projection in the maximal electroshock model of epilepsy—II. Pathways from substantia nigra pars lateralis and adjacent peripeduncular area to the dorsal midbrain

Lesion evidence suggests that the superior colliculus is essential for mediating the anticonvulsant properties of nigral suppression in the electroshock model of epilepsy. However, our companion paper [Redgrave et al. (1991) Neuroscience 46, 379–390] established that the region of dorsal midbrain where bicuculline was most effective in suppressing tonic hindlimb extension did not correspond well with the known distribution of nigrotectal terminals. The purpose of the present anatomical study was, therefore, to investigate in more detail ventral midbrain connections to the dorsal midbrain anticonvulsant zone in rat. Small injections (10–20 nl) of a 1% solution of wheatgerm agglutinin conjugated with horseradish peroxidase were made specifically into the region of dorsal midbrain where bicuculline was maximally effective. Numerous retrogradely labelled cells were found in substantia nigra pars lateralis and adjacent peripeduncular area but not in substantia nigra pars reticulata. Retrogradely labelled cells were also located in ventral zona incerta. When wheatgerm agglutinin-horseradish peroxidase injections were made into lateral substantia nigra, a region of anterogradely transported reaction product characteristic of nerve terminals was observed in the caudolateral deep layers and underlying reticular tissue; this area corresponded well to the dorsal midbrain anticonvulsant zone. These data suggest that, in the electroshock model of epilepsy, direct connections between substantia nigra pars lateralis and adjacent peripeduncular area and the dorsal midbrain anticonvulsant zone could be critical for mediating the anticonvulsant properties previously attributed to substantia nigra pars reticulata. During the course of this study, anterograde projections from substantia nigra pars lateralis and adjacent peripeduncular area to both superficial and intermediate layers of the ipsilateral superior colliculus were noted. Additional experiments using retrograde transport of the fluorescent tracer Fast Blue confirmed these projections.

CNS projections to the pterygopalatine parasympathetic preganglionic neurons in the rat: a retrograde transneuronal viral cell body labeling study

The retrograde transneuronal viral cell body labeling method was used to study the CNS nuclei that innervate the parasympathetic preganglionic neurons which project to the pterygopalatine ganglion. Small injections of a suspension of pseudorabies virus (PRV) were made in the pterygopalatine ganglion of rats and after 4 days their brains were processed for immunohistochemical detection of PRV. Some of the tissues were stained with a dual immunofluorescence method that permitted the visualization of PRV and neurotransmitter enzyme or serotonin immunoreactivity in the same cell. Retrograde cell body labeling was detected in the ipsilateral ventrolateral medulla oblongata in the region that has been termed the superior salivatory nucleus. This area was the same region that was retrogradely labeled after Fluoro-Gold dye injections in the pterygopalatine ganglion. Retrograde transneuronally infected cell bodies that provide putative afferent inputs to the pytergopalatine parasympathetic preganglionic neurons were mapped throughout the brain. In the medulla oblongata, transneuronally labeled neurons were seen in the nucleus tractus solitarii, dorsomedial part of the spinal trigeminal nucleus and gigantocellular reticular nucleus. In most experiments, some A1 catecholamine cells and serotonin neurons of the raphe magnus, raphe pallidus, raphe obscurus, and parapyramidal nuclei were labeled. In the pons, labeled cells were found in the parabrachial nucleus, A5 catecholamine cell group, and non-catecholamine part of the subcoeruleus region. In the midbrain, cell body labeling was located in the central gray matter and retrorubral field. In the diencephalon, labeling was found mainly in the hypothalamus. The areas included the lateral hypothalamic area, lateral preoptic area, dorsomedial and paraventricular hypothalamic nuclei, and ventral zona incerta. Contralateral second order cell body labeling was seen in the tuberomammillary nucleus of the hypothalamus. Some of these cells were histidine decar☐ylase-immunoreactive. In the forebrain, the bed nucleus of the stria terminalis, substantia innominata, and an area of the cerebral cortex called the amygdalopiriform transition zone were labeled.

Ibotenic acid lesions of the lateral substantia nigra restore visual orientation behavior in the hemianopic cat

Transection of non-tectotectal fibers in the caudal one-half of the commissure of the superior colliculus restores visual orienting to a cat previously rendered hemianopic by a large unilateral visual cortical lesion. Other observations related to this recovery phenomenon (i.e., the Sprague effect) have suggested that the caudal commissural fibers whose destruction produces the recovery 1) are contralateral afferents to the superior colliculus on the side of the cortical lesion, and 2) profoundly influence visuo-motor processing in this superior colliculus. We performed anatomical and behavioral experiments to determine which of the more than 40 contralateral collicular afferents are directly involved in the Sprague effect. To guide subsequent behavioral studies, we performed a pilot anatomical experiment in which we injected WGA-HRP unilaterally into one superior colliculus at identical retinotopic loci in each of a pair of cats. One cat was normal (control), and the other (experimental) had previously received a caudal transection of the collicular commissure. Quantitative comparison of the retrograde labeling in collicular afferents revealed that a number of mesencephalic regions contain neurons that project to the colliculus via the caudal collicular commissure. Additional collicular injections of WGA-HRP demonstrated the exact location and distribution of collicular afferent neurons within these nuclei. In the behavioral experiments, we attempted to replicate the Sprague effect by destroying the neurons giving rise to the axons in the caudal collicular commissure. Ibotenic acid lesions of these neurons were performed in cats that were hemianopic following the removal of the contralateral visual cortex. Small lesions of a "critical zone" in the rostro-lateral substantia nigra pars reticulata and possibly the overlying ventral zona incerta consistently produced a visual recovery whereas lesions of the other collicular afferents did not. Paradoxically, large nigral lesions that also included the critical zone did not result in a recovery. A conceptual framework for these findings involving striato-nigro-tecto-preoculomotor interactions is presented.

L-Glutamate stimulation of the zona incerta in the rat decreases heart rate and blood pressure

Microinjections of l-glutamate into the zona incerta of pentobarbital anesthetized rats caused decreases in blood pressure and heart rate. The bradycardic response was reduced by≈70% after i.v. administration of atropine methyl nitrate. After combined muscarinic and β-adrenergic blockade the bradycardic response was reduced to 90% of the control value. This suggests that the bradycardia was mediated primarily by activating the vagal outflow. Blood pressure decreases elicited after pharmacological blockade of the heart with both atropine and timolol were≈50% of the control values. This indicates that the zona incerta is also capable of altering stroke volume and/or inhibiting the sympathetic outflow controlling the peripheral blood vessels. By using an injectate containing l-glutamate mixed with [ 3H] l-glutamate and subsequent analysis of autoradiographic tissue sections, we have determined that the most reactive site is the region of the ventral zona incerta.

Afferents to the zona incerta in the rat: a combined retrograde and anterograde study.

In a first set of experiments, the retrograde transport of horseradish peroxidase (HRP) was utilized to investigate the afferent projections to the zona incerta (ZI) in the hooded rat. HRP was introduced in its crystalline form into various sectors of the ZI of seven subjects. The largest contingent of afferents arises from the following centers: the cingulate and somatosensory cortices, central amygdaloid nucleus, ventromedial hypothalamic nucleus, posterior thalamic nucleus, anterior pretectal nucleus, peripeduncular area, deep and intermediate layers of the superior colliculus, dorsal and ventral parabrachial nuclei, principal and interpolar trigeminal subnuclei, and cuneate nucleus. Other centers less systematically or more sparsely labeled were the lateral hypothalamic area, ventrobasal complex, lateral geniculate nucleus pars ventralis, medial geniculate nucleus, interstitial nucleus of Cajal, Darkschewitsch nucleus, perirubral fields, cuneiform, tegmental pedunculopontine, and deep mesencephalic reticular nuclei, pontine reticular nucleus pars oralis, lateral and interpositus cerebellar nuclei, and gracile nucleus. In a second set of experiments, an anterograde tracer (WGA-HRP) was injected in several centers projecting to the ZI in order to localize their terminal fields within this structure. It has been thus possible to distinguish a ventral zone (ventral sector of pars caudalis and pars ventralis) in which the somesthetic (somatosensory cortex, trigeminal complex, and dorsal column nuclei (DCN), collicular, and cerebellar projections terminate, from a dorsal zone (pars dorsalis) to which a limbic input (cingulate cortex and ventromedial hypothalamic nucleus) is directed. In most cases, the labeled terminal fields consisted of well-delimited, narrow bands disposed obliquely, parallel to the cerebral peduncle or the internal capsule. The contingent of somatosensory afferents is relatively large and there is a high degree of overlapping between the different somatosensory terminal fields within the ventral ZI. This suggests a participation of this structure in the treatment of somesthetic information and/or in the transmission of noxious stimuli.

The ascending fiber projections from the principal sensory trigeminal nucleus in the rat.

AbstractPersisting reports of uncrossed secondary trigeminothalamic pathways originating from the principal sensory trigeminal nucleus (PrV) are based mainly on data obtained from surgically induced lesions analyzed by methods other than reduced silver impregnation techniques. After complete stereotaxic or direct surgical lesions of PrV, degenerating fibers proceed ventrally and rostrally from the nucleus and cross the midline in the rostral pons, completing their decussation caudal to nucleus interpeduncularis. These fibers form a large trigeminal lemniscus that ascends through the midbrain dorsomedial to the smaller medial lemniscus. PrV fibers terminate in the posterior thalamic nucleus and throughout the medial two‐thirds of the ventrobasal thalamic complex (VBm) contralateral to the side of the lesion. Connections with the ventral part of zona incerta were also found similar to those reported for the medial lemniscus.Another fiber system proceeds dorsad from the parvicellular reticular formation in the PrV region and terminates on cells of the ipsi‐and contralateral motor trigeminal nuclei and the adjacent contralateral parvicellular reticular formation. Differential lesions indicate that these “intertrigeminal” commissural connections arise chiefly from the parvicellular reticular formation that lies between PrV and the motor trigeminal nucleus.These experiments, which also included selective lesions of dorsal and rostral portions of PrV, failed to produce any evidence supporting the existence of an uncrossed principal sensory trigeminothalamic pathway in the rat. While selective, ventral zona incerta PrV connections can be demonstrated, no PrV intralaminar projections appear to exist. Initial findings show that comparable fully decussated PrV–VBm connections also exist in the guinea pig but that some ipsilaterally ascending fibers occur in monkeys (Smith, '72). These and other recent data demonstrate that phyletic neural variations exist in the PrV‐thalamic projections in various mammalian species.