A Topographic Atlas of the Human Brainstem in the Ponto-Mesencephalic Junction Plane

The human brainstem harbors neuronal aggregates that ensure the maintenance of several vital functions. It also acts as a major relay structure for the neuronal information that travels between the cerebral cortex, the cerebellum and the spinal cord. As such, this relatively small portion of the human brain houses a multitude of ascending and descending fibers that course among numerous nuclei whose exact boundaries are still uncertain. Such a large number of nuclei and fiber tracts confined to a relatively small and compact brain region imposes upon the brainstem a highly complex cytoarchitectonic organization that still needs to be deciphered. The present work provides a topographic atlas of the human brainstem composed of 45 anatomical plates, each containing a pair of adjacent sections stained with Cresyl Violet and Luxol Fast Blue to help delineating brainstem nuclei and fiber tracts, respectively. The plates, which cover the entire midbrain, pons and medulla oblongata, are composed of equally-spaced sections referenced and aligned parallel to the ponto-mesencephalic junction rather than the fastigium or the obex. This topographic landmark is particularly suitable for neurosurgical interventions aiming at specific nuclei of the mesencephalic tegmentum. In complement, we provide 8 anatomical plates containing adjacent sections stained for choline acetyltransferase and Luxol Fast Blue, taken through the midbrain and the pons. This open access atlas of the human brainstem is intended to assist neuroanatomists, neurosurgeons and neuropathologists in their work.

Microsurgical Anatomy of Safe Entry Zones on the Ventrolateral Brainstem: A Morphometric Study

Surgery of the brainstem is challenging due to the complexity of the area with cranial nerve nuclei, reticular formation and ascending and descending fibers. Safe entry zones are required to reach the intrinsic lesions of the brainstem. The aim of this study was to provide detailed measurements for anatomical landmark zones of the ventrolateral surface of the human brainstem related to previously described safe entry zones. In this study, 53 complete and 34 midsagittal brainstems were measured using a stainless caliper with an accuracy of 0.01 mm. The distance between the pontomesencephalic and bulbopontine sulci was measured as 26.94 mm. Basilar sulcus-lateral side of pons (origin of the fibers of the trigeminal nerve) distance was 17.23 mm, transverse length of the pyramid 5.42 mm and vertical length of the pyramid 21.36 mm. Lateral mesencephalic sulcus was 12.73 mm, distance of the lateral mesencephalic sulcus to the oculomotor nerve 13.85 mm and distance of trigeminal nerve to the upper tip of pyramid 17.58 mm. The transverse length for the inferior olive at midpoint and vertical length were measured as 5.21 mm and 14.77 mm, consequently. The thickness of the superior colliculus was 4.36 mm, the inferior colliculus 5.06 mm; length of the tectum was 14.5 mm and interpeduncular fossa 11.26 mm. Profound anatomical knowledge and careful analysis of preoperative imaging are mandatory before surgery of the brainstem lesions. The results presented in this study will serve neurosurgeons operating in the brainstem region.

Diversity of molecularly defined spinal interneurons engaged in mammalian locomotor pattern generation

Mapping the expression of transcription factors in the mouse spinal cord has identified ten progenitor domains, four of which are cardinal classes of molecularly defined, ventrally located interneurons that are integrated in the locomotor circuitry. This review focuses on the properties of these interneuronal populations and their contribution to hindlimb locomotor central pattern generation. Interneuronal populations are categorized based on their excitatory or inhibitory functions and their axonal projections as predictors of their role in locomotor rhythm generation and coordination. The synaptic connectivity and functions of these interneurons in the locomotor central pattern generators (CPGs) have been assessed by correlating their activity patterns with motor output responses to rhythmogenic neurochemicals and sensory and descending fibers stimulations as well as analyzing kinematic gait patterns in adult mice. The observed complex organization of interneurons in the locomotor CPG circuitry, some with seemingly similar physiological functions, reflects the intricate repertoire associated with mammalian motor control and is consistent with high transcriptional heterogeneity arising from cardinal interneuronal classes. This review discusses insights derived from recent studies to describe innovative approaches and limitations in experimental model systems and to identify missing links in current investigational enterprise.

Cat's medullary reticulospinal and subnucleus reticularis dorsalis noxious neurons form a coupled neural circuit through collaterals of descending axons

Animals and human beings sense and react to real/potential dangerous stimuli. However, the supraspinal mechanisms relating noxious sensing and nocifensive behavior are mostly unknown. The collateralization and spatial organization of interrelated neurons are important determinants of coordinated network function. Here we electrophysiologically studied medial medullary reticulospinal neurons (mMRF-RSNs) antidromically identified from the cervical cord of anesthetized cats and found that 1) more than 40% (79/183) of the sampled mMRF-RSNs emitted bifurcating axons running within the dorsolateral (DLF) and ventromedial (VMF) ipsilateral fascicles; 2) more than 50% (78/151) of the tested mMRF-RSNs with axons running in the VMF collateralized to the subnucleus reticularis dorsalis (SRD) that also sent ipsilateral descending fibers bifurcating within the DLF and the VMF. This percentage of mMRF collateralization to the SRD increased to more than 81% (53/65) when considering the subpopulation of mMRF-RSNs responsive to noxiously heating the skin; 3) reciprocal monosynaptic excitatory relationships were electrophysiologically demonstrated between noxious sensitive mMRF-RSNs and SRD cells; and 4) injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin evidenced mMRF to SRD and SRD to mMRF projections contacting the soma and proximal dendrites. The data demonstrated a SRD-mMRF network interconnected mainly through collaterals of descending axons running within the VMF, with the subset of noxious sensitive cells forming a reverberating circuit probably amplifying mutual outputs simultaneously regulating motor activity and spinal noxious afferent input. The results provide evidence that noxious stimulation positively engages a reticular SRD-mMRF-SRD network involved in pain-sensory-to-motor transformation and modulation.

Multiparametric Corticofugal Modulation of Collicular Duration-Tuned Neurons: Modulation in the Amplitude Domain

The subcortical auditory nuclei contain not only neurons tuned to a specific frequency but also those tuned to multiple parameters characterizing a sound. All these neurons are potentially subject to modulation by descending fibers from the auditory cortex (corticofugal modulation). In the past, we electrically stimulated cortical duration-tuned neurons of the big brown bat, Eptesicus fuscus, and found that its collicular duration-tuned neurons were corticofugally modulated in the frequency and time (duration) domains. In the current paper, we report that they were also corticofugally modulated in the amplitude (intensity) domain. We found the following collicular changes evoked by focal cortical electric stimulation. 1) Corticofugal modulation in the amplitude domain differed depending on whether recorded collicular neurons matched in best frequency (BF) with stimulated cortical neurons. BF-matched neurons decreased their thresholds, whereas BF-unmatched neurons increased their thresholds: the larger the BF difference between the recorded collicular and stimulated cortical neurons, the larger the threshold increase. 2) In general, the dynamic range for amplitude coding was larger in the inferior colliculus than in the auditory cortex. BF-matched neurons increased their dynamic ranges and response magnitude, whereas BF-unmatched neurons decreased them. 3) Single duration-tuned neurons were simultaneously modulated by cortical electric stimulation in the amplitude, frequency and time domains. 4) Corticofugal modulation in these three domains indicates that the contrast of the neural representation of repeatedly delivered sound stimuli is increased.

Synaptic Differentiation of Single Descending Fibers Studied by Triple Intracellular Recording in the Frog Spinal Cord

Dityatev, Alexander E. and H. Peter Clamann. Synaptic differentiation of single descending fibers studied by triple intracellular recording in the frog spinal cord. J. Neurophysiol. 79: 763–768, 1998. Evoked excitatory postsynaptic potentials (EPSPs) were simultaneously intracellularly recorded in two lumbar motoneurons located in spinal segments 8–10 in response to intraaxonal stimulation of a descending fiber. Their mean amplitudes, paired-pulse facilitation, and short- and long-term posttetanic potentiation were compared to reveal possible functional differences among synapses formed by one axon on different postsynaptic targets. The mean amplitudes of EPSPs recorded in two motoneurons were significantly different in most experiments. This amplitude difference was related to the location of motoneurons in that it was twofold larger in motoneurons separated by >1 mm than in motoneurons located within 200 μm of one another and also that the amplitude of EPSPs recorded in motoneurons located in the tenth segment was regularly smaller than the amplitude recorded in the ninth segment. The estimation of binomial model parameters suggests that the difference in mean EPSP amplitude was due mostly to differences in the maximal number of quanta prepared for release (binomial parameter N) and in mean release probability rather than to differences in quantal size. The ability of connections formed by a single axon on different motoneurons to undergo use-dependent synaptic modulations was different on scales of milliseconds, seconds, and tens of minutes as revealed by the measurements of effects of paired-pulse and tetanic stimulation. The difference in magnitude of short-term posttetanic potentiation in connections formed by a single descending axon was significantly correlated with the difference in mean probability of release in these connections. Thus our data revealed a functional nonuniformity of synapses formed by individual descending fibers on widely separated motoneurons, most likely innervating different muscles. This process can be one of the mechanisms by which a fine descending control of recruitment of motoneuronal populations is achieved.