Evolution of neuronal systems of suprasegmental motor control

The study of supraspinal systems of motor control in a series of vertebrates by electroanatomical methods shows that certain key features of reticulo-motoneuronal projection persist throughout the scale of evolution from Cyclostomata to primates. There is a particularly marked similarity between the monosynaptic reticulo-motoneuronal EPSPs in primitive animals and in the advanced quadrupeds: amphibians, reptiles, and mammals. Certain general principles governing the maturation of derivatives of the reticulo-spinal system, namely the vestibulo-spinal and rubro-spinal projections, can be discussed. The most marked changes occurred in the development of the mammalian cortico-spinal system. The properties of the conducting system and synaptic connections with the spinal motoneurons differ considerably in the series rodents—carnivores—primates. In this survey the similarities and differences between the pyramidal and nonpyramidal monosynaptic projections to motoneurons in primates and the role of brain-stem structures in the mechanism of cortico-extrapyramidal control are discussed.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Leningrad. Translated from Neirofiziologiya, Vol. 4, No. 5, pp. 453–470, September–October, 1972.     

Effects of repetitive stimulation of the locus coeruleus on spinal inhibitory responses to suprasegmental stimulation in cats

Effects of repetitive stimulation of the locus coeruleus on spinal responses to activation of cortico-, reticulo-, and vestibulospinal tracts were studied in decerebellate cats anesthetized with chloralose. Descending influences of these structures were assessed from changes in amplitude of extensor and flexor monosynaptic discharges or from the magnitude of postsynaptic potentials recorded from the corresponding motoneurons. Stimulation of the motor cortex or modullary reticular formation as a rule evoked two-component inhibitory responses in extensor motoneurons and excitatory-inhibitory responses in flexor motoneurons. Stimulation of locus coeruleus effectively depressed the amplitude of the late component and, to a lesser degree, that of the early component of inhibition arising after stimulation of the cerebral cortex or reticular formation. During stimulation of the locus coeruleus no marked changes were found in inhibitory responses evoked by vestibulospinal influences in flexor motoneurons, and also in excitatory responses arising after stimulation of the above-mentioned descending pathways in both groups of motoneurons.     

Postural interneurons in the abdominal nervous system of lobster

The nature of the synaptic relationship between 7 identified postural interneurons and 5 pairs of superficial motoneurons was examined by obtaining dual intracellular recordings from interneuron-motoneuron pairs in the lobster 2nd abdominal ganglion. For six different interneuron-motoneuron pairs EPSPs recorded from motoneurons occurred with a short (1 to 3 ms) fixed latency following each presynaptic spike recorded from the interneuron. This suggests that there is a monosynaptic relationship between these interneurons and motoneurons. Monosynaptic pathways accounted for 27% of all excitatory connections. Preliminary evidence indicates that the monosynaptic potentials are mediated by an excitatory chemical synapse since: all IPSPs occurred with latencies greater than 5 ms, there was no evidence for electrical coupling, and one of the interneurons produced facilitating PSPs. A majority of all monosynaptic connections were made by two of the flexion producing interneurons (FPIs), 201 and 301. The synaptic outputs of these FPIs were similar in that both made monosynaptic connections with a different bilaterally homologous pair of motoneurons. Both also produced larger EPSPs and more vigorous spiking in contralateral members of the bilateral motoneuron pairs. A previous study demonstrated that interneurons 201 and 301 are the only postural interneurons yet identified that express motor programs indistinguishable from command neurons. Taken together, these results suggest that certain intersegmental interneurons share properties with command neurons and driver neurons, and that there may not be a sharp morphological or functional distinction between these two cell types.     

Postural interneurons in the abdominal nervous system of lobster

The multisegmented abdomen of crayfish and lobster assumes a variety of postures as components of different behavioral acts. Experimentally these postures can be maintained by activating any of a number of premotor positioning interneurons. The pathways by which the motor output in two or more segments is coordinated were here investigated for a small group of identified postural interneurons whose somata lie in the 2nd abdominal ganglion (A2). Stimulation of all postural interneurons examined evokes a motor output in other abdominal ganglia through which the axon of the neuron passes as well as in the ganglion of origin (ganglion containing the neuron's cell body). The spread of motor excitation away from the originating ganglion occurs via two general pathways. In the first pathway connections to postural motoneurons are made directly by processes of the postural interneuron which pass into ganglia distal to the originating ganglion. Examples of this are shown for two flexion producing interneurons (FPIs) 201 and 301. Each of these FPIs makes monosynaptic connections with motoneurons in A2 and with a homologous set of motoneurons in A3. All postural interneurons fired a set of corollary discharge interneurons (CDIs) whose activities were recorded from the abdominal connectives. Two FPIs, 202 and 301, and a third interneuron, 503, produced motor outputs in ganglia to which they did not project. The motor specificity established in A2 by stimulation of FPIs 202 and 301 (whose axons pass caudally) was preserved in more rostral ganglia, such as A1. Therefore, different sets of CDIs can be specifically recruited to spread the same motor program that is initiated in the originating ganglion to ganglia that do not receive projections from the stimulated postural interneuron. CDIs, in addition, have the capacity to elicit motor programs in distal ganglia that are markedly different from that expressed in the ganglion of origin. For example, although 503 produced an inhibitory output in the abdominal ganglia that it innervated (A1 and A2), a flexion response was generated by it in more caudal ganglia. The caudal flexion response was mediated in part through a monosynaptic activation of FPI 201 and through other unidentified CDIs. Thus, the interneuronal circuitry for postural control is composed of numerous components, some of which have regional control over different portions of the abdominal nerve cord. Depending upon the required movement, select components are coactivated, either serially or in parallel, to effect a variety of spatially distinct positions.     

Reticulofugal influences of interneurons in the lateral region of gray matter of the cat spinal cord

Responses of lumbar interneurons located in the most lateral regions of Rexed's laminae IV–VII to stimulation of the medial longitudinal bundle and gigantocellular reticular nucleus of medullary pyramids, red nucleus, and peripheral nerves were investigated in cats anesthetized with pentobarbital. Stimulation of the reticulospinal fibers evoked monosynaptic excitation of many interneurons specialized for transmitting activity of the lateral descending systems, but not of peripheral afferents. Convergence of excitatory influences of all three descending systems (cortico-, rubro-, and reticulospinal) was observed on some cells of this group. In addition, monosynaptic "reticular" E PSPs appeared in interneurons transmitting activity of group Ia muscle fibers and in some interneurons of the flexor reflex afferent system. Stimulation of reticulospinal fibers evoked IPSPs in some neurons of this last group. Neurons not exposed to reticulofugal influences (both specialized neurons and interneurons of segmental reflex arcs) were located chiefly in the dorsal zones of the region studied. Recordings were also obtained from single fibers of the lateral reticulospinal tracts (conduction velocity from 26 to 81 m/sec).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 5, No. 5, pp. 525–536, September–October, 1973.     

Lack of evidence for cell death among avian spinal cord interneurons during normal development and following removal of targets and afferents.

Chick embryos and posthatched chicks were examined at several ages for the presence of pyknotic interneurons in the lumbar spinal cord. Because no pyknotic interneurons were found, direct cell counts of healthy interneurons were carried out and a comparison made between early- and late-stage embryos and hatchlings. There was no decrease in the number of interneurons in the ventral intermediate gray matter of the spinal cord between embryonic day (E) 8 and 2 weeks posthatching (PH) or in the dorsal horn between E10 and 2 weeks PH. To study whether interneuron survival is regulated by targets or afferents, a situation known to exist in other developing neural populations, early embryos were subjected to (1) removal of one limb, resulting in the loss of lateral motor column motoneurons and dorsal root ganglion sensory afferents; (2) transection of the thoracic spinal cord, thereby removing both descending afferents and rostral targets of spinal interneurons, or (3) a combination of the two operations. No reductions in interneuron numbers were found as a result of these operations. Furthermore, morphometric analysis also revealed no change in neuronal size following these experimental manipulations. By contrast, there was a slight decrease in the total area of spinal gray matter that was most prominent in the dorsal region following limb bud removal. Our results indicate (1) that spinal interneurons fail to exhibit the massive naturally occurring death of postmitotic neurons that has been observed for several other populations of spinal neurons, and (2) spinal interneurons appear to be relatively resistant to induced cell death following the removal of substantial numbers of afferent inputs and targets.     

Lack of evidence for cell death among avian spinal cord interneurons during normal development and following removal of targets and afferents

Chick embryos and posthatched chicks were examined at several ages for the presence of pyknotic interneurons in the lumbar spinal cord. Because no pyknotic interneurons were found, direct cell counts of healthy interneurons were carried out and a comparison made between early-and late-stage embryos and hatchlings. There was no decrease in the number of interneurons in the ventral intermediate gray matter of the spinal cord between embryonic day (E) 8 and 2 weeks posthatching (PH) or in the dorsal horn between E10 and 2 weeks PH. To study whether interneuron survival is regulated by targets or afferents, a situation known to exist in other developing neural populations, early embryos were subjected to (1) removal of one limb, resulting in the loss of lateral motor column motoneurons and dorsal root ganglion sensory afferents; (2) transection of the thoracic spinal cord, thereby removing both descending afferents and rostral targets of spinal interneurons, or (3) a combination of the two operations. No reductions in interneuron numbers were found as a result of these operations. Furthermore, morphometric analysis also revaled no change in neuronal size following these experimental manipulations. By contrast, there was a slight decrease in the total area of spinal gray matter that was most prominent in the dorsal region following limb bud removal. Our results indicate (1) that spinal interneurons fail to exhibit the massive naturally occurring death of postmitotic neurons that has been observed for several other populations of spinal neurons, and (2) spinal interneurons appear to be relatively resistant to induced cell death following the removal of substantial numbers of afferent inputs and targets.     

Some problems of projections and actions of cortico- and rubro-spinal fibres.

A review of a number of known, partly known and to be established properties of the cortico- and rubro-spinal tract systems in relation to: (1) multiple projections of individual neurones, or functional subgroups of neurones in the motor cortex and in the red nucleus, (2) identification of spinal target cells of these neurones, and (3) the mechanisms of interactions between the two systems.     

Effect of removal of the cerebellum on vestibular responses of neurons in various descending tracts in cats

Responses of vestibulo-, reticulo-, and rubro-spinal neurons of decerebrate cats to tilting in the frontal plane were investigated. In cats with an intact cerebellum only dynamic responses, i.e., responses during movement (with a small after-effect), were observed. In decerebellate cats responses of the rubro-spinal neurons were absent, and those of the reticulo-spinal neurons were greatly reduced. Dynamic responses of vestibulo-spinal neurons also were considerably reduced, but static responses appeared in many neurons.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 4, No. 3, pp. 303–310, May–June, 1972.     

Peripheral specification of Ia synaptic input to motoneurons innervating foreign target muscles

Muscle sensory neurons, called Ia afferents, make monosynaptic connections with functionally related sets of motoneurons in the spinal cord. Previous work has suggested that peripheral target muscles play a major role in determining the central connections of Ia afferents with motoneurons. Here, we ask whether motoneurons can also be influenced by their target muscles in terms of the monosynaptic input they receive from Ia afferents, by transplanting thoracic motoneurons into the lumbosacral spinal cord so that they innervate foreign muscles. Three or four segments of thoracic neural tube from stage 14-15 chicken embryos were transplanted to the lumbosacral region of stage 16-17 embryos, and electrophysiological recordings were made from transplanted motoneurons after the embryos had reached stage 38-40. Transplanted thoracic motoneurons innervated limb muscles and received monosynaptic inputs from Ia afferents. These connections were not random: Most of the connections were formed between Ia afferents and motoneurons projecting to the same muscle (homonymous connections). Few aberrant connections were found although the anatomical distribution of afferents in the transplant indicated that they had ample opportunity to contact inappropriate motoneurons. We conclude that although peripheral target cues are not sufficient to respecify an already committed motoneuron (turn a thoracic motoneuron into a lumbosacral motoneuron), they do provide sufficient information for Ia afferent input to be functionally correct.     

Synaptic potentials of motoneurons of the masseter muscle

Postsynaptic potentials of 93 motoneurons of the masseter muscle evoked by stimulation of different branches of the trigeminal nerve were studied. Stimulation of the most excitable afferent fibers of the motor nerve of the masseter muscle evoked monosynaptic EPSPs with a latent period of 1.2–2.0 msec, changing into action potentials when the strength of stimulation was increased. A further increase in the strength of stimulation produced an antidromic action potential in the motoneurons with a latent period of 0.9 msec. In some motoneurons polysynaptic EPSPs and action potentials developed following stimulation of the motor nerve to the masseter muscle. The ascending phase of synaptic and antidromic action potentials was subdivided into IS and SD components, while the descending phase ended with definite depolarization and hyperpolarization after-potentials. Stimulation of cutaneous branches of the trigeminal nerve, and also of the motor nerve of the antagonist muscle (digastric) evoked IPSPs with a latent period of 2.7–3.5 msec in motoneurons of the masseter muscle. These results indicate the existence of functional connections between motoneurons of the masseter muscle and its proprioceptive afferent fibers, and also with proprioceptive afferent fibers of the antagonist muscle and cutaneous afferent fibers.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 3, pp. 262–268, November–December, 1969.     

Monosynaptic control of spinal motoneurons from different levels of the brain

In experiments on cats and monkeys it is established that reticulo-, rubro-, and corticomotoneuronal influences are characterized by a number of common features: 1) they are produced by fast conducting fibers of the descending tracts; 2) they do not attain the critical level needed for AP generation; and 3) they are caused by implication of synapses that are predominantly located on dendrites of the motoneurons. Results of experiments carried out on lampreys and rats indicate that reticulo-motoneuronal monosynaptic projections emerge already at the earliest stages of vertebrate evolution and retain their significance in mammals. The data of research on supraspinal influences during ontogenesis indicate early development of descending stem projections. This enables us to regard cerebro-motoneuronal monosynaptic connections as an important component of supraspinal control of motoneurons, a component whose functional role is in large measure determined by interaction with other synaptic inputs of the motoneuron.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 2, pp. 203–215, March–April, 1970.     

Quantitative analysis of inputs to somatostatin-immunoreactive descending interneurons in the myenteric plexus of the guinea-pig small intestine

Somatostatin immunoreactivity occurs in a specific subgroup of cholinergic descending interneurons in the myenteric plexus of the guinea-pig small intestine. In the present work, we made light- and electron-microscopic investigations of chemically defined inputs to these neurons, in order that the origins of the connections of other neurons with them could be deduced. Somatostatin-immunoreactive synapses and close contacts were found on the cell bodies and filamentous processes of somatostatin neurons; these were 84% of all inputs. It is thus confirmed that this class of interneuron forms chains that project anally. Descending interneurons with immunoreactivity for nitric oxide synthase provided 14% of inputs to somatostatin-immunoreactive descending interneurons. An antiserum against a calcium-binding protein, calbindin, was used as marker for the majority of intrinsic primary afferent neurons, AH/Dogiel type II neurons; this class of neurons provided only 2.5% of the inputs to somatostatin-immunoreactive descending interneurons. We conclude that somatostatin-immunoreactive descending interneurons are involved in the conduction of impulses distally along the full length of the small intestine, but receive only a minor input from calbindin-immunoreactive primary afferent neurons.     

Specification of synaptic connections between sensory and motor neurons in the developing spinal cord

Experimental studies of mechanisms underlying the specification of synaptic connections in the monosynaptic stretch reflex of frogs and chicks are described. Sensory neurons innervating the triceps brachii muscles of bullfrogs are born throughout the period of sensory neurogenesis and do not appear to be related clonally. Instead, the peripheral targets of these sensory neurons play a major role in determining their central connections with motoneurons. Developing thoracic sensory neurons made to project to novel targets in the forelimb project into the brachial spinal cord, which they normally never do. Moreover, these foreign sensory neurons make monosynaptic excitatory connections with the now functionally appropriate brachial motoneurons. Normal patterns of neuronal activity are not necessary for the formation of specific central connections. Neuromuscular blockade of developing chick embryos with curare during the period of synaptogenesis still results in the formation of correct sensory-motor connections. Competitive interactions among the afferent fibers also do not seem to be important in this process. When the number of sensory neurons projecting to the forelimb is drastically reduced during development, each afferent still makes central connections of the same strength and specificity as normal. These results are discussed with reference to the development of retinal ganglion cells and their projections to the brain. Although many aspects of the two systems are similar, patterned neural activity appears to play a much more important role in the development of the visual pathway than in the spinal reflex pathway described here.     

Synaptic processes in neurons of the cervical enlargement of the cat spinal cord during stimulation of propriospinal pathways of the dorsolateral tract

Responses of motoneurons and interneurons of the cervical enlargement of the cat spinal cord were studied by a microelectrode technique during selective stimulation of propriospinal fibers of the dorsolateral tract of the lateral white column. The long descending and ascending pathways were blocked by preliminary (10–16 days earlier) hemisection of the spinal cord cranially and caudally to the segments studied. Stimulation of the dorsolateral tract at a distance of 15–25 mm from the site of recording evoked complex postsynaptic potentials consisting of several successive waves in the motoneurons. The character of the PSPs was not clearly linked with the function of the motoneurons. By their latent periods the components of the PSPs could be placed in three groups. The "primary" components were reproduced in response to stimulation at 50–100/sec whereas the "secondary" and "tertiary" components were weakened or blocked. It is postulated that the "primary" components are evoked through monosynaptic connections between propriospinal fibers of the dorsolateral tract and motoneurons of the forelimb muscles, while the late components are evoked through polysynaptic pathways, including segmental interneurons. Many of these interneurons, located in the ventral horn and intermediate zone, were strongly excited during stimulation of the dorsolateral tract.A. A. Bogomolets' Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 5, No. 1, pp. 61–69, January–February, 1973.     

Distribution of terminals of primary afferent fibers connected polysynaptically with motoneurons in the frog spinal cord

Parallel intracellular recordings of potentials in primary afferent fibers (in the region of their entry into the spinal cord) and motoneurons were made in experiments on an isolated perfused preparation of frog spinal cord preserving its connections with hind limb nerves. It was shown by injection of horseradish peroxidase through a microelectrode inserted into the fiber that fast-conducting cutaneous, tendon, and muscular afferents connected polysynaptically with motoneurons reach only the upper or middle third of the dorsal horn. Terminal branches of these fibers are characterized by numerous short terminal twigs given off at short distances apart from larger collaterals. Terminal boutons and en passant contacts, stained with horseradish peroxidase, were found on bodies of interneurons. In some cases, trans-synaptic staining of interneurons was found to take place. It is suggested that peroxidase-labeled interneurons form axo-axonal synapses with primary afferents.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 14, No. 6, pp. 615–621, November–December, 1982.     

Postsynaptic effects evoked by activation of long propriospinal pathways in cervical spinal neurons in cats

Effects induced in motoneurons and interneurons of the cervical enlargements of the cat spinal cord by stimulation of the lateral and ventral funiculi at the lower thoracic level were studied under conditions producing degeneration of fibers of descending brain systems. Stimulation of this sort evoked PSPs (mainly of mixed character) in 57 of 90 motoneurons tested. In nine motoneurons the primary response consisted of monosynaptic EPSPs evoked by activity of fibers of the lateral funiculus, and in the rest it consisted of polysyanptic (at least disynaptic) EPSPs and IPSPs. Polysynaptic effects arising in the neuron in response to stimulation of the lateral and ventral funiculi usually differed only quantitatively. The intensity of excitatory synaptic action on motoneurons of the proximal muscle (especially thoracid) was much greater than that on motoneurons of distal muscles. Nearly all motoneurons with no synaptic action belonged to the latter group. Stimulation of the lateral and ventral funculi facilitated synaptic action induced in motoneurons by stimulation of high-threshold segmental afferents and led to excitation of interneurons located in the vectral quadrant, and had no effect on interneurons in the dorsal regions of gray matter. These effects are regarded mainly as the result of excitation of long ascending propriospinal pathways in the cervical parts of the cord; it is also postulated that some of them are evoked by the arrival of activity along collaterals of descending propiospinal pathways to the neurons in this region.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 4, pp. 339–347, July–August, 1979.     

Cytoarchitectural organization of the electromotor system in the electric catfish (Malapterurus electricus)

Summary The cytoarchitectural organization of the electromotor system of the electric catfish (Malapterurus electricus) was investigated in order to obtain insight into the neuronal reorganization accompanying the functional transition of a presumptive previous motor system to an electromotor system eliciting electric organ discharge. The electric catfish possesses two giant electromotoneurons situated within the rostral spinal cord. Intracellular dye injections have revealed the enormous extension of the dendritic tree of electromotoneurons. About 50 primary dendrites span the entire lateral funicle and intermediate grey matter, and reveal an extensive contralateral projection. The giant dendritic tree (1.2 mm in rostrocaudal direction) presumably receives inputs from all ascending and descending pathways of the spinal cord. Electromotoneurons and motoneurons receive the same type of fibre inputs, and electromotoneurons and interneurons are connected through common presynaptic elements. The innervation pattern of the electromotoneurons and spinal motoneurons is similar. Synaptic terminals with round synaptic vesicles often reveal chemical contacts and gap junctions. Furthermore, dendrites of the two electromotoneurons form juxtapositions (ephapses) with each other and also with spinal interneurons. Our results suggest that the two electromotoneurons are homologous to median (primary) spinal motoneurons and are the central structures of the electromotor system within the central nervous system of the electric catfish. A high capability of information processing can be attributed to the giant dendritic trees from functional considerations. This presumably enables the electromotoneurons to elicit an electric organ discharge in different behavioural contexts with a minimum of functional reorganization.     

Synaptic activation of thoracic interneurons by reticulospinal fibers of the lateral funiculus

Synaptic responses of different functional groups of interneurons in segments T10 and T11 to stimulation of the ipsilateral and contralateral medullary reticular formation were investigated in anesthetized cats with only the ipsilateral lateral funiculus remaining intact. Activation of reticulospinal fibers of the lateral funiculus with conduction velocities of 30–100 m/sec was shown to induce short-latency and, in particular, monosynptic EPSPs in all types of cells tested: in interneurons excited by group Ia muscle afferents, in cells activated only by high-threshold cutaneous and muscle afferents (afferents of the flexor reflex), in cells activated mainly by descending systems, and, to a lesser degree, in neurons connected with low-threshold cutaneous afferents. These cell populations are located mainly in the central and lateral parts of Rexed's lamina VII. Most neurons in laminae I–V of the dorsal horn, except six cells located in the superficial layers of the dorsal horn, received no reticulofugal influences. The functional organization of connections of the lateral reticulospinal tract with spinal neurons is discussed and compared with the analogous organization of the medial reticulospinal tract, and also of the "lateral" (cortico- and rubrospinal) descending systems.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 2, pp. 150–161, March–April, 1978.     

Monosynaptic rabies virus reveals premotor network organization and synaptic specificity of cholinergic partition cells

Movement is the behavioral output of neuronal activity in the spinal cord. Motor neurons are grouped into motor neuron pools, the functional units innervating individual muscles. Here we establish an anatomical rabies virus-based connectivity assay in early postnatal mice. We employ it to study the connectivity scheme of premotor neurons, the neuronal cohorts monosynaptically connected to motor neurons, unveiling three aspects of organization. First, motor neuron pools are connected to segmentally widely distributed yet stereotypic interneuron populations, differing for pools innervating functionally distinct muscles. Second, depending on subpopulation identity, interneurons take on local or segmentally distributed positions. Third, cholinergic partition cells involved in the regulation of motor neuron excitability segregate into ipsilaterally and bilaterally projecting populations, the latter exhibiting preferential connections to functionally equivalent motor neuron pools bilaterally. Our study visualizes the widespread yet precise nature of the connectivity matrix for premotor interneurons and reveals exquisite synaptic specificity for bilaterally projecting cholinergic partition cells.