Upper brainstem cholinergic neurons project to ascending and descending circuits.

BACKGROUND: Based on their anatomical location, rostral projections of nuclei are classified as ascending circuits, while caudal projections are classified as descending circuits. Upper brainstem neurons participate in complex information processing and specific sub-populations preferentially project to participating ascending or descending circuits. Cholinergic neurons in the upper brainstem have extensive collateralizations in both ascending and descending circuits; however, their single-cell projection patterns remain unclear because of the lack of comprehensive characterization of individual neurons. RESULTS: By combining fluorescent micro-optical sectional tomography with sparse labeling, we acquired a high-resolution whole-brain dataset of pontine-tegmental cholinergic neurons (PTCNs) and reconstructed their detailed morphology using semi-automatic reconstruction methods. As the main source of acetylcholine in some subcortical areas, individual PTCNs had abundant axons with lengths up to 60 cm and 5000 terminals and innervated multiple brain regions from the spinal cord to the cortex in both hemispheres. Based on various collaterals in the ascending and descending circuits, individual PTCNs were grouped into four subtypes. The morphology of cholinergic neurons in the pedunculopontine nucleus was more divergent, whereas the laterodorsal tegmental nucleus neurons contained richer axonal branches and dendrites. In the ascending circuits, individual PTCNs innervated the thalamus in three different patterns and projected to the cortex via two separate pathways. Moreover, PTCNs targeting the ventral tegmental area and substantia nigra had abundant collaterals in the pontine reticular nuclei, and these two circuits contributed oppositely to locomotion. CONCLUSIONS: Our results suggest that individual PTCNs have abundant axons, and most project to various collaterals in the ascending and descending circuits simultaneously. They target regions with multiple patterns, such as the thalamus and cortex. These results provide a detailed organizational characterization of cholinergic neurons to understand the connexional logic of the upper brainstem.

Midbrain, Pons, and Medulla: Anatomy and Syndromes.

The anatomy of the brainstem is complex. It contains numerous cranial nerve nuclei and is traversed by multiple tracts between the brain and spinal cord. Improved MRI resolution now allows the radiologist to identify a higher level of anatomic detail, but an understanding of functional anatomy is crucial for correct interpretation of disease. Brainstem syndromes are most commonly due to occlusion of the posterior circulation or mass effect from intrinsic space-occupying lesions. These syndromes can have subtle imaging findings that may be missed by a radiologist unfamiliar with the anatomy or typical manifesting features. This article presents the developmental anatomy of the brainstem and discusses associated pathologic syndromes. Congenital and acquired syndromes are described and correlated with anatomic locations at imaging, with diagrams to provide a reference to aid in radiologic interpretation. ©RSNA, 2019.

Genetic identification of a neural circuit that suppresses appetite.

Appetite suppression occurs after a meal and in conditions when it is unfavourable to eat, such as during illness or exposure to toxins. A brain region proposed to play a role in appetite suppression is the parabrachial nucleus, a heterogeneous population of neurons surrounding the superior cerebellar peduncle in the brainstem. The parabrachial nucleus is thought to mediate the suppression of appetite induced by the anorectic hormones amylin and cholecystokinin, as well as by lithium chloride and lipopolysaccharide, compounds that mimic the effects of toxic foods and bacterial infections, respectively. Hyperactivity of the parabrachial nucleus is also thought to cause starvation after ablation of orexigenic agouti-related peptide neurons in adult mice. However, the identities of neurons in the parabrachial nucleus that regulate feeding are unknown, as are the functionally relevant downstream projections. Here we identify calcitonin gene-related peptide-expressing neurons in the outer external lateral subdivision of the parabrachial nucleus that project to the laterocapsular division of the central nucleus of the amygdala as forming a functionally important circuit for suppressing appetite. Using genetically encoded anatomical, optogenetic and pharmacogenetic tools, we demonstrate that activation of these neurons projecting to the central nucleus of the amygdala suppresses appetite. In contrast, inhibition of these neurons increases food intake in circumstances when mice do not normally eat and prevents starvation in adult mice whose agouti-related peptide neurons are ablated. Taken together, our data demonstrate that this neural circuit from the parabrachial nucleus to the central nucleus of the amygdala mediates appetite suppression in conditions when it is unfavourable to eat. This neural circuit may provide targets for therapeutic intervention to overcome or promote appetite.

A negative association between brainstem pontine grey-matter volume, well-being and resilience in healthy twins

Background: Associations between well-being, resilience to trauma and the volume of grey-matter regions involved in affective processing (e.g., threat/reward circuits) are largely unexplored, as are the roles of shared genetic and environmental factors derived from multivariate twin modelling. Methods: This study presents, to our knowledge, the first exploration of well-being and volumes of grey-matter regions involved in affective processing using a region-of-interest, voxel-based approach in 263 healthy adult twins (60% monozygotic pairs, 61% females, mean age 39.69 yr). To examine patterns for resilience (i.e., positive adaptation following adversity), we evaluated associations between the same brain regions and well-being in a trauma-exposed subgroup. Results: We found a correlated effect between increased well-being and reduced grey-matter volume of the pontine nuclei. This association was strongest for individuals with higher resilience to trauma. Multivariate twin modelling suggested that the common variance between the pons volume and well-being scores was due to environmental factors. Limitations: We used a cross-sectional sample; results need to be replicated longitudinally and in a larger sample. Conclusion: Associations with altered grey matter of the pontine nuclei suggest that basic sensory processes, such as arousal, startle, memory consolidation and/or emotional conditioning, may have a role in well-being and resilience.

Angular and metric analysis of the neural structures in the cerebellopontine angle.

INTRODUCTION: The cerebellopontine angle (CPA) is a subarachnoid space in the lateral aspect of the posterior fossa. In this study, we propose a complementary analysis of the CPA from the cerebellopontine fissure. METHODS: We studied 50 hemi-cerebelli in the laboratory of neuroanatomy and included a description of the CPA anatomy from the cerebellopontine fissure and its relationship with the flocculus and the 5th, 6th, 7th, and 8th cranial nerves (CN) origins. RESULTS: The average distance from the 5th CN to the mid-line (ML) was 19.2 mm, 6th CN to ML was 4.4 mm, 7-8 complex to ML was 15.8 mm, flocculus to ML was 20.5 mm, and flocculus to 5th CN was 11.5 mm, additionally, and the diameter of the flocculus was 9.0 mm. The angle between the vertex in the flocculus and the V CN and the medullary-pontine line was 64.8 degrees. DISCUSSION: The most common access to the CPA is through the retrosigmoid-suboccipital region and this approach can be done with the help of an endoscope. The anatomy of origins of neural structures tends to be preserved in cases of CPA lesions. CONCLUSION: Knowledge of the average distances between the neural structures in the cerebellar-pontine fissure and the angular relationships between these structures facilitates the use of surgical approaches such as microsurgery and endoscopy.

Endoscopic approach-routes in the posterior fossa cisterns through the retrosigmoid keyhole craniotomy: an anatomical study.

Endoscopy in cerebellopontine angle surgery is an increasingly used technique. Despite of its advantages, the shortcomings arising from the complex anatomy of the posterior fossa are still preventing its widespread use. To overcome these drawbacks, the goal of this study was to define the anatomy of different endoscopic approaches through the retrosigmoid craniotomy and their limitations by surgical windows. Anatomical dissections were performed on 25 fresh human cadavers to describe the main approach-routes. Surgical windows are spaces surrounded by neurovascular structures acting as a natural frame and providing access to deeper structures. The approach-routes are trajectories starting at the craniotomy and pointing to the lesion, passing through certain windows. Twelve different windows could be identified along four endoscopic approach-routes. The superior route provides access to the structures of the upper pons, lower mesencephalon, and the upper neurovascular complex through the suprameatal, superior cerebellar, and infratrigeminal windows. The supratentorial route leads to the basilar tip and some of the suprasellar structures via the ipsi- and contralateral oculomotor and dorsum sellae windows. The central endoscopic route provides access to the middle pons and the middle neurovascular complex through the inframeatal, AICA, and basilar windows. The inferior endoscopic route is the pathway to the medulla oblongata and the lower neurovascular complex through the accessory, hypoglossal, and foramen magnum windows. The anatomy and limitations of each surgical windows were described in detail. These informations are essential for safe application of endoscopy in posterior fossa surgery through the retrosigmoid approach.

Bayesian segmentation of brainstem structures in MRI.

In this paper we present a method to segment four brainstem structures (midbrain, pons, medulla oblongata and superior cerebellar peduncle) from 3D brain MRI scans. The segmentation method relies on a probabilistic atlas of the brainstem and its neighboring brain structures. To build the atlas, we combined a dataset of 39 scans with already existing manual delineations of the whole brainstem and a dataset of 10 scans in which the brainstem structures were manually labeled with a protocol that was specifically designed for this study. The resulting atlas can be used in a Bayesian framework to segment the brainstem structures in novel scans. Thanks to the generative nature of the scheme, the segmentation method is robust to changes in MRI contrast or acquisition hardware. Using cross validation, we show that the algorithm can segment the structures in previously unseen T1 and FLAIR scans with great accuracy (mean error under 1mm) and robustness (no failures in 383 scans including 168 AD cases). We also indirectly evaluate the algorithm with a experiment in which we study the atrophy of the brainstem in aging. The results show that, when used simultaneously, the volumes of the midbrain, pons and medulla are significantly more predictive of age than the volume of the entire brainstem, estimated as their sum. The results also demonstrate that the method can detect atrophy patterns in the brainstem structures that have been previously described in the literature. Finally, we demonstrate that the proposed algorithm is able to detect differential effects of AD on the brainstem structures. The method will be implemented as part of the popular neuroimaging package FreeSurfer.

Surgical approaches to IV ventricle--anatomical study.

PURPOSE: Knowledge of anatomy of the IV ventricle is basic to surgical approach of any kind of lesion in its compartment as well as for those located in its neighborhood. The purpose of this study is to demonstrate the surgical approach options for the IV ventricle, based on the step by step dissection of anatomical specimens. METHODS: Fifty formalin-fixed specimens provided were the material for this study. The dissections were performed in the microsurgical laboratory in Gainesville, Florida, USA. RESULTS: The IV ventricle in a midline sagittal cut shows a tent-shaped cavity with its roofs pointing posteriorly and the floor formed by the pons and the medulla. The superior roof is formed by the superior cerebellar peduncles laterally and the superior medullary velum on the midline. The inferior roof is formed by the tela choroidea, the velum medullary inferior, and the nodule. The floor of the IV ventricle has a rhomboid shape. The rostral two thirds are related to the pons, and the caudal one third is posterior to the medulla. The median sulcus divides the floor in symmetrical halves. The sulcus limitans runs laterally to the median sulcus, and the area between the two sulci is called the median eminence. The median eminence contains rounded prominence related to the cranial nucleus of facial, hypoglossal, and vagal nerves. The lateral recesses are extensions of the IV ventricle that opens into the cerebellopontine cistern. The cerebellomedullary fissure is a space between the cerebellum and the medulla and can be used as a surgical corridor to the IV ventricle. CONCLUSIONS: We obtained in this study a didactic dissection of the different anatomical structures, whose recognition is important for addressing the IV ventricle lesions.

Anatomical location of the medial lemniscus and spinothalamic tract at the pons in the human brain: a diffusion tensor tractography study.

Using diffusion tensor tractography, we investigated the anatomical location of medial lemniscus (ML) and spinothalamic tract (STT) at pons. We recruited 47 healthy volunteers. Evaluation of the anatomical location of ML and STT was performed using the highest probabilistic location at the upper, middle, and lower pons. According to findings, MLs were located around the middle to medial one-third, between midline and lateral boundary of pons in the pontine tegmentum and STTs were located posterolaterally to ML.

In vivo characterization of the vestibulo-cochlear nerve motion by MRI.

The motion of the vestibulo-cochlear nerve (VCN) was quantified at the level of the cerebello-pontine angle in 28 healthy volunteers enrolled in a prospective study performed on a 3T MRI scanner. A phase contrast MRI (PCMRI) sequence was used. The VCN was divided into a cisternal part and a meatic part, both of which were measured for motion in the cranio-caudal (CC) and antero-posterior (AP) directions. Motion was cardiac-cycle-dependent in these two directions. The meatic VCN motion was delayed compared to the cisternal VCN motion. In the CC direction, the mean amplitude of the cisternal VCN motion was twice larger than the mean amplitude of the meatic VCN motion (0.37+/-0.14 mm versus 0.17+/-0.08 mm). In the AP direction, the mean amplitude of the cisternal VCN was 0.19+/-0.08 mm versus 0.16+/-0.14 mm for the meatic VCN. We used an "oscillating string" to explain the VCN motion. Reproducibility tests have shown small variations in measurements of the CC motion. PCMRI can be used to assess the VCN motion at the level of the cerebello-pontine angle.

Role of Neph2 in pontine nuclei formation in the developing hindbrain.

Nuclei are anatomical units of the central nervous system (CNS). Their formation sets the structural basis for the functional organization of the brain, a process known as nucleogenesis. In the present study, we investigated the role of the transmembrane immunoglobulin superfamily molecule Neph2 in the nucleogenesis of the pontine nucleus (PN). Neph2 expression is turned on in migrating PN neurons only after they enter the presumptive nuclear region. Neph2 knockdown disrupted the nuclear organization of PN presumably by changing the migratory behavior of PN neurons inside the nuclear region. Moreover, overexpression of the cytoplasmic region of Neph2, which can sequester intracellular signaling of endogenous Neph2, resulted in similar phenotypes. Overall, these results suggest Neph2 is involved in the nucleogenesis of the PN through the control of neuronal migration inside the nucleus.

Stereological evaluation of the volume and volume fraction of newborns' brain compartment and brain in magnetic resonance images.

PURPOSE: Brain development in early life is thought to be critical period in neurodevelopmental disorder. Knowledge relating to this period is currently quite limited. This study aimed to evaluate the volume relation of total brain (TB), cerebrum, cerebellum and bulbus+pons by the use of Archimedes' principle and stereological (point-counting) method and after that to compare these approaches with each other in newborns. METHODS: This study was carried out on five newborn cadavers mean weighing 2.220 ± 1.056 g with no signs of neuropathology. The mean (±SD) age of the subjects was 39.7 (±1.5) weeks. The volume and volume fraction of the total brain, cerebrum, cerebellum and bulbus+pons were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods and by the use of fluid displacement technique. RESULTS: The mean (±SD) TB, cerebrum, cerebellum and bulbus+pons volumes by fluid displacement were 271.48 ± 78.3, 256.6 ± 71.8, 12.16 ± 6.1 and 2.72 ± 1.6 cm3, respectively. By the Cavalieri principle (point-counting) using sagittal MRIs, they were 262.01 ± 74.9, 248.11 ± 68.03, 11.68 ± 6.1 and 2.21 ± 1.13 cm3, respectively. The mean (± SD) volumes by point-counting technique using axial MR images were 288.06 ± 88.5, 275.2 ± 83.1, 19.75 ± 5.3 and 2.11 ± 0.7 cm3, respectively. There were no differences between the fluid displacement and point-counting (using axial and sagittal images) for all structures (p > 0.05). CONCLUSION: This study presents the basic data for studies relative to newborn's brain volume fractions according to two methods. Stereological (point-counting) estimation may be accepted a beneficial and new tool for neurological evaluation in vivo research of the brain. Based on these techniques we introduce here, the clinician may evaluate the growth of the brain in a more efficient and precise manner.

Pretecto- and ponto-cerebellar pathways to the pigeon oculomotor cerebellum follow a zonal organization.

Both birds and mammals have relatively large forebrains and cerebella. In mammals, there are extensive sensory-motor projections to the cerebellum through the pontine nuclei originating from several parts of the cerebral cortex. Similar forebrain-to-cerebellum pathways exist in birds, but the organization of this circuitry has not been studied extensively. Birds have two nuclei at the base of the brainstem that are thought to be homologous to the pontine nuclei of mammals, the medial and lateral pontine nuclei (PM, PL). Additionally, birds are unique in that they have a pretectal nucleus called the medial spiriform nucleus (SpM) that, like the pontine nuclei, also receives projections from the forebrain and projects to the oculomotor cerebellum (OCb; folia VI to VIII). The OCb also receives input from the pretectal nucleus lentiformis mesencephali (LM), which analyzes visual optic flow information resulting from self-movement. In this study, we used single or double injections of fluorescent tracers to study the organization of these inputs from PM, PL, SpM and LM to the OCb in pigeons. We found that these inputs follow a zonal organization. The most medial zone in the OCb, zone A1, receives bilateral inputs from the lateral SpM, PL and LM. Zones A2 and C receive a bilateral projection from the medial SpM, and a mostly contralateral projection from PM and LM. We discuss how the pathway to zone A1 processes mainly visuo-motor information to spinal premotor areas, whereas the pathways to zone A2/C processes somato-motor and visuo-motor information and may have a feedback/modulatory role.

Microsurgical and endoscopic anatomy of Liliequist's membrane and the prepontine membranes: cadaveric study and clinical implications.

BACKGROUND: Liliequist's membrane is mostly described as having a diencephalic leaf, mesencephalic leaf, and diencephalic-mesencephalic leaves in the literature. Also different descriptions of the prepontine membranes were reported. In this study, we visualized the regular structural forms of membranes without disturbing any attachments and defined infrachiasmatic and prepontine safety zones. We discussed the clinical significance of these structures. MATERIALS AND METHODS: The study was carried out on 24 adult human cadavers at the Morgue Specialization Department of the Forensic Medicine Institution following the initial autopsy examination. Liliequist's membrane and the prepontine membranes were explored after retraction of the frontal lobes. Dissections were performed under the operative microscope. A 0- and 30-degree, 2.7-mm angled rigid endoscope (Aesculap, Tuttlingen, Germany) was advanced through the prepontine cistern from the natural holes of membranes, or small holes were opened without damaging the surrounding structures. RESULTS: The basal arachnoid membrane (BAM) continued as Liliequist's membrane (LM) without any distinct separation in all specimens. The LM coursed over the posterior clinoids and split into two leaves as the diencephalic leaf (DL) and mesencephalic leaf (ML) in 18 specimens; the medial pontomesencephalic membrane (MPMM) coursed anterolaterally as a continuation of the ML and attached to the medial surfaces of the fifth and sixth nerves, joining with the lateral pontomesencephalic membrane (LPMM), which was also a posterolateral continuation of the ML in all specimens. The medial pontomedullar membrane (MPMdM) and lateral pontomedullar membrane (LPMdM) were observed in 21 specimens. The MPMdM membrane was a continuation of the MPMM, and the LPMdM was a continuation of the LPMM in all 21 specimens. CONCLUSION: We observed that the LM is a borderless continuation of the BAM. The MPMM and LPMM split from the ML without any interruptions. The MPMdM and LPMdM were a single membrane continuing from the MPMM and LPMM. We determined infrachiasmatic and prepontine areas that can be important for inferior surgical approaches.

The fate of spontaneous synchronous rhythms on the cerebrocerebellar loop.

How does the cerebellum participate in neocortical rhythms? Neocortical signals destined for the cerebellum are integrated in the pontine nuclei (PN) with cerebellar output signals via a direct, reciprocal feedback loop with the cerebellar nuclei (CN). The present study investigated the fate of two spontaneously occurring rhythms in rat neocortex under ketamine anesthesia-slow wave activity at around 1 Hz and gamma oscillations-within this pontonuclear feedback loop. Coordinated oscillatory neuronal activity was studied using simultaneous multineuron recordings in primary motor cortex (M1), PN, and lateral CN. It was revealed that slow burst firing-known in neocortex as "up and down states"-is readily conveyed within the pontonuclear feedback loop and thus engages the entire cerebropontocerebellothalamic loop. In contrast, gamma band synchronous oscillations reached only the PN under the present experimental conditions. Surprisingly, many CN single units were actually found to oscillate in the gamma range, but they completely failed to synchronize with other units in either CN or PN. These results show firstly that slow concerted activity can readily engage the entire cerebrocerebellar loop. Secondly, they raise the possibility that fast gamma oscillations may be incompatible with cerebellar processing and get blocked out. Future studies in behaving animals are needed to answer the question whether signals coded in gamma band frequency are converted to another carrier code using the feedback control exerted by the pontonuclear loop.

Mapping of neural pathways that influence diaphragm activity and project to the lumbar spinal cord in cats.

During breathing, the diaphragm and abdominal muscles contract out of phase. However, during other behaviors (including vomiting, postural adjustments, and locomotion) simultaneous contractions are required of the diaphragm and other muscle groups including abdominal muscles. Recent studies in cats using transneuronal tracing techniques showed that in addition to neurons in the respiratory groups, cells in the inferior and lateral vestibular nuclei (VN) and medial pontomedullary reticular formation (MRF) influence diaphragm activity. The goal of the present study was to determine whether neurons in these regions have collateralized projections to both diaphragm motoneurons and the lumbar spinal cord. For this purpose, the transneuronal tracer rabies virus was injected into the diaphragm, and the monosynaptic retrograde tracer Fluoro-Gold (FG) was injected into the Th13-L1 spinal segments. A large fraction of MRF and VN neurons (median of 72 and 91%, respectively) that were infected by rabies virus were dual-labeled by FG. These data show that many MRF and VN neurons that influence diaphragm activity also have a projection to the lumbar spinal cord and thus likely are involved in coordinating behaviors that require synchronized contractions of the diaphragm and other muscle groups.

Ultrasonography of the fetal brainstem: a biometric and anatomical, multioperator, cross-sectional study of 913 fetuses of 21-36 weeks of gestation.

OBJECTIVES: To establish the ultrasonographic fetal growth charts of the pons and the vermis/pons ratio on a multioperator basis in low-risk pregnancies and provide a detailed description of the anatomical and ultrasonographic criteria of normal brainstem growth. METHODS: A prospective, multicenter, multioperator, ultrasonographic study was conducted on 913 fetuses aged 21-36 weeks. The anteroposterior diameter of the pons and the greatest vermal height were measured to establish a growth chart, using a mid-sagittal plane with a posterior transfontanellar approach. The LMS semiparametric statistical method was used to construct the growth charts. Three morphological structures were also examined: the pons arch and its echostructure, the bulbo-protuberential sulcus and the primary vermal fissure. RESULTS: The anteroposterior diameter of the pons and the greatest vermal height were measured in 96.7% of cases. The anteroposterior diameter of the pons and vermis increased linearly with gestational age. The vermis/pons ratio was stable during pregnancy. CONCLUSION: We have drawn the growth charts for the pons and vermis during pregnancy and described the normal ultrasound morphology of the brainstem. Knowledge of these morphological and biometric data could facilitate early screening for pontocerebellar hypoplasia.

Anatomy of the brainstem: a gaze into the stem of life.

The brainstem has an ectodermal origin and is composed of 4 parts: the diencephalon, mesencephalon, pons, and medulla oblongata. It serves as the connection between the cerebral hemispheres with the medulla and the cerebellum and is responsible for basic vital functions, such as breathing, heartbeat blood pressure, control of consciousness, and sleep. The brainstem contains both white and gray matter. The gray matter of the brainstem (neuronal cell bodies) is found in clumps and clusters throughout the brainstem to form the cranial nerve nuclei, the reticular formation, and pontine nuclei. The white matter consists of fiber tracts (axons of neuronal cells) passing down from the cerebral cortex--important for voluntary motor function--and up from peripheral nerves and the spinal cord--where somatosensory pathways travel--to the highest parts of the brain. The internal structure of brainstem, although complex, presents a systematical arrangement and is organized in 3 laminae (tectum, tegmentum, and basis), which extend its entire length. The motor pathway runs down through the basis, which is located at the most anterior part. The cranial nerve nuclei are settled into the middle layer (the tegmentum), just in front of the 4th ventricle and are placed, from medial to lateral, on the basis of their function: somatic motor, visceral motor, visceral sensory, and somatic sensory. All the somatosensory tracts run upward to the thalamus crossing the tegmentum in front of the cranial nerve nuclei. The tectum, formed by the quadrigeminal plate and the medullary velum, contains no cranial nuclei, no tracts and no reticular formation. The knowledge of precise anatomical localization of a lesion affecting the brainstem is crucial in neurological diagnosis and, on this basis, is essential to be familiar with the location of the mayor tracts and nuclei appropriately. Nowadays, current magnetic resonance imaging techniques, although still macroscopic, allow the fine internal structure of the brainstem to be viewed directly and make it possible to locate the main intrinsic structures that justify the symptoms of the patient. In this article we discuss the anatomy of the brainstem and highlight the features and landmarks that are important in interpreting magnetic resonance imaging.

Interpeduncular Sulcus Approach to the Posterolateral Pons.

OBJECTIVE: In this article, we describe a new safe entry point for the posterolateral pons. METHODS: To show the adjacent anatomy and measure the part of the interpeduncular sulcus that can be safely accessed, we first performed a review of the literature regarding the pons anatomy and its surgical approaches. Thereafter, 1 human cadaveric head and 15 (30 sides) human brainstems with attached cerebellums were bilaterally dissected with the fiber microdissection technique. A clinical correlation was made with an illustrative case of a dorsolateral pontine World Health Organization grade I astrocytoma. RESULTS: The safe distance for accessing the interpeduncular sulcus was found to extend from the caudal end of the lateral mesencephalic sulcus to the point at which the intrapontine segment of the trigeminal nerve crosses the interpeduncular sulcus. The mean distance was 8.2 mm (range, 7.15-8.85 mm). Our interpeduncular sulcus safe entry zone can be exposed through a paramedian infratentorial supracerebellar approach. When additional exposure is required, the superior portion of the quadrangular lobule of the cerebellar hemispheric tentorial surface can be removed. In the presented case, surgical resection of the tumor was performed achieving a gross total resection, and the patient was discharged without neurologic deficit. CONCLUSIONS: The interpeduncular sulcus safe entry zone provides an alternative direct route for treating intrinsic pathologic entities situated in the posterolateral tegmen of the pons between the superior and middle cerebellar peduncles. The surgical corridor provided by this entry point avoids most eloquent neural structures, thereby preventing surgical complications.