Dendritic Targeting in the Leg Neuropil of Drosophila: The Role of Midline Signalling Molecules in Generating a Myotopic Map

Neural maps are emergent, highly ordered structures that are essential for organizing and presenting synaptic information. Within the embryonic nervous system of Drosophila motoneuron dendrites are organized topographically as a myotopic map that reflects their pattern of innervation in the muscle field. Here we reveal that this fundamental organizational principle exists in adult Drosophila, where the dendrites of leg motoneurons also generate a myotopic map. A single postembryonic neuroblast sequentially generates different leg motoneuron subtypes, starting with those innervating proximal targets and medial neuropil regions and producing progeny that innervate distal muscle targets and lateral neuropil later in the lineage. Thus the cellular distinctions in peripheral targets and central dendritic domains, which make up the myotopic map, are linked to the birth-order of these motoneurons. Our developmental analysis of dendrite growth reveals that this myotopic map is generated by targeting. We demonstrate that the medio-lateral positioning of motoneuron dendrites in the leg neuropil is controlled by the midline signalling systems Slit-Robo and Netrin-Fra. These results reveal that dendritic targeting plays a major role in the formation of myotopic maps and suggests that the coordinate spatial control of both pre- and postsynaptic elements by global neuropilar signals may be an important mechanism for establishing the specificity of synaptic connections.     

Influence of interganglionic interactions on steroid-mediated dendritic reorganization and death of proleg motor neurons during metamorphosis in Manduca sexta

In Manduca sexta, the larval abdominal prolegs and their muscles degenerate at pupation. The proleg motor neurons undergo a period of dendritic regression, after which a specific subset of them dies. The surviving motor neurons undergo dendritic outgrowth during pupal-adult development, and most die after adult emergence. All of these events are regulated hormonally by ecdysteroids and juvenile hormone, but interactions of the motor neurons with other cells may potentially contribute as well. To investigate the possible influence of interganglionic neural interactions, we chronically isolated individual abdominal ganglia by severing the adjacent rostral and caudal connectives in the larval stage. Subsequent metamorphic changes in proleg motor neurons were examined in the isolated ganglia and ganglia adjacent to the isolated ganglia. Two abnormalities were observed: (1) some imprecision in the timing of motor neuron death, both at pupation and after adult emergence, and (2) the growth of ectopic neurites outside the neuropil boundaries during pupal-adult development (in ganglia with or without neuromas caused by connective transections). Other aspects of proleg motor neuron metamorphosis, including the segment-specific death of motor neurons at pupation, were the same as that in intact and sham-operated insects. Thus, interganglionic interactions appear to play a relatively minor role in the steroid-mediated metamorphic transformation of proleg motor neurons. © 1994 John Wiley & Sons, Inc.     

Intersegmental sensory tracts and contralateral motor neurons in the leg ganglia of the spider Cupiennius salei Keys

Summary Cobalt filling into spider legs reveals plurisegmental receptor endings and the plurisegmental origin of motor neurons. Motor neuron dendrites are organized into two domains, one interacting with plurisegmental receptors, the other arborizing within the lateral neuropil of the leg neuromere. The intersegmental organization of both motor and sensory elements supports behavioural studies demonstrating inhibitory connections between legs.     

Patterning and organization of motor neuron dendrites in the Drosophila larva

Precise patterns of motor neuron connectivity depend on the proper establishment and positioning of the dendritic arbor. However, how different motor neurons orient their dendrites to selectively establish synaptic connectivity is not well understood. The Drosophila neuromuscular system provides a simple model to investigate the underlying organizational principles by which distinct subclasses of motor neurons orient their dendrites within the central neuropil. Here we used genetic mosaic techniques to characterize the diverse dendritic morphologies of individual motor neurons from five main nerve branches (ISN, ISNb, ISNd, SNa, and SNc) in the Drosophila larva. We found that motor neurons from different nerve branches project their dendrites to largely stereotyped mediolateral domains in the dorsal region of the neuropil providing full coverage of the receptive territory. Furthermore, dendrites from different motor neurons overlap extensively, regardless of subclass, suggesting that repulsive dendrite-dendrite interactions between motor neurons do not influence the mediolateral positioning of dendritic fields. The anatomical data in this study provide important information regarding how different subclasses of motor neurons organize their dendrites and establishes a foundation for the investigation of the mechanisms that control synaptic connectivity in the Drosophila motor circuit.     

Early ontogeny of the vagus nerve: an analysis of the medulla oblongata and cervical spinal cord of the postnatal rat.

Retrograde transport of cholera toxin conjugated with horseradish peroxidase in the postnatal rat has revealed remarkable features of dendritic fields of vagal motor neurons in the medulla oblongata and cervical spinal cord during the period of early development (0-10 days). At birth, vagal motor neurons in the dorsal motor nucleus of the vagus, nucleus ambiguus, nucleus retroambigualis, nucleus dorsomedials and the spinal nucleus of the accessory nerve are small with relatively few, unbranched processes. The span of the dendritic tree is much smaller than that found in adult animals. By the postnatal Day 2 there are marked changes in the soma as well as in the dendritic tree of these neurons. There is dispersion of the cell bodies within the neuropil as well as an expansion of the total area of the brain stem occupied by these motor neurons and their dendritic processes which show extensive growth and branching. By postnatal Day 3 the most extensive proliferation of these neurons is seen and appears to represent the peak of dendritic growth of vagal motor neurons such that the area occupied by the dendritic tree of a single neuron is three times that seen in an adult rat. This proliferation gradually decreased during the subsequent seven days of early development (i.e. Days 4-10) so that by Day 10 the dendritic span of vagal motor neurons was reduced to about twice the adult size. This growth progressively decreased from Days 10 to 30 at which time adult levels were reached. Ultrastructural examination of these horseradish peroxidase labeled dendrites showed a positive correlation between the number of dendritic processes and the number of axo-dendritic synapses. This was accompanied by an increase in the number of identifiable synaptic junctions. These morphological complexities observed during the period of early development of vagal motor neurons indicate that the vagus nerve undergoes dramatic changes during the period of early development including the establishment of numerous synaptic contacts between vagal afferents and efferents in the brainstem. A number of these changes occur in developing dendritic fields of vagal motor neurons during the first three days of neonatal life. It is reasonable to assume that developmental abnormalities during this "critical period" could produce significant functional changes in the pattern of respiration as well as in the control of airway smooth muscle.     

Organization of motor neurons innervating the proboscis musculature in Drosophila melanogaster meigen (diptera : Drosophilidae)

The present study addresses the question as to how the motor neurons involved in feeding in Drosophila melanogaster Meigen (Diptera : Drosophilidae) are organized. The motor neurons have been visualized both by Golgi-silver impregnation and by intramuscular injection of horseradish peroxidase, and analyzed in light of the existing information on taste sensory system and the feeding behaviour. The motor neurons have been broadly classified into the following types: labial nerve motor neurons, pharyngeal nerve motor neurons, and accessory pharyngeal nerve motor neurons, depending on the nerve through which their axons exit. The arborization of all the motor neurons is confined to the suboesophageal ganglion (SOG). All of them have predominantly ipsilateral and some contralateral arborizations. Their dendrites predominantly occupy the ventral region of the neuropil of the SOG and partially overlap the taste sensory projections, thereby providing an opportunity for interaction with the taste sensory input. The pharyngeal motor neurons arborize more extensively in the ventral tritocerebram, anteroventral. and mid-ventral neuropil, whereas the dendritic fields of labial motor neurons are confined to the mid-ventral neuropil. There is a functional segregation in motor neuron organization: cibarial muscles involved in sucking are innervated by pharyngeal motor neurons, while the proboscis muscles involved in positioning, of the proboscis are innervated by labial motor neurons. We have also observed projections of the stomodaeal nerve in the tritocerebrum.     

Remodeling of an identified motoneuron during metamorphosis: hormonal influences on the growth of dendrites and axon terminals

During metamorphosis of the tobacco hawkmoth Manduca sexta, the femoral depressor motoneuron (FeDe MN) undergoes remodeling of its dendrites and motor terminals. Previous studies have established that remodeling of MNs during metamorphosis is mediated by the same hormones that control metamorphosis: the ecdysteroids and juvenile hormone (JH). During the pupal stage, the ecdysteroids promote adult-specific growth of MNs in the absence of JH, but JH or its synthetic mimics can interfere with ecdysteroid-mediated growth if applied during early sensitive periods. Hence, the application of a JH mimic (JHM) either systemically or locally to a target muscle has been used to distinguish those aspects of motor-terminal remodeling that are controlled by ecdysteroid action on the CNS from those that are influenced by ecdysteroid action on the peripheral targets. Here, we have extended the analysis of central and peripheral hormonal influences on MN remodeling by injecting JHM locally into the CNS thus altering the hormonal environment of the FeDe MN soma without altering the hormonal environment of its target muscle. Our results demonstrate that adult dendritic growth and motor-terminal growth can be experimentally uncoupled, suggesting that each is regulated independently. JHM application to the CNS perturbed dendritic growth, but had no measurable impact on motor-terminal growth. Peripheral actions of ecdysteroids, therefore, appear sufficient to promote the development of adult-specific motor terminals but not the development of an adult-specific dendritic arbor.     

Afferent innervation shapes the dendritic branching pattern of the Medial Giant Interneuron in grasshopper embryos raised in culture

In the adult grasshopper the Medial Giant Interneuron (MGI) receives synaptic input from the peripheral sensory neurons of the cercus. We prevented this innervation in grasshopper embryos by cutting off one or both cerci at a stage when the first sensory axons are just beginning to reach the central nervous system (CNS), and the MGI has not yet formed its mature branching pattern. Following this operation the embryos were raised in vitro for 3–9 days, and the MGI injected with the fluorescent dye Lucifer Yellow to determine its morphology. The development of the deprived cells was then compared to that of the normal MGI (described in M. Shankland and C. S. Goodman, 1982, Develop. Biol., 92, 483–500) and of cultured, but unoperated, controls to ascertain whether these presynaptic axons influence the embryonic growth and branching of the MGI's dendrites. The results of these experiments show that dendrite formation is enhanced in regions of the neuropil containing sensory axon terminals and that the afferents exert their influence locally on restricted portions of the branching structure. The enhanced growth of innervated dendrites appears to occur at the expense of dendritic outgrowth elsewhere, suggesting that the growing dendrites may be competing for a limited supply of some cellular component necessary for continued growth. Thus, the MGI's final branching pattern is at least partially dictated by the spatial distribution of presynaptic axons within the embryonic nervous system.     

The dorsomedial nuclear group of cranial nerves in the frog.

The dorsomedial motor nuclei were demonstrated by the cobalt-labeling technique applied to the so-called somatic motor cranial nerves. The motoneurons constituting these nuclei are oval-shaped and smaller than the motoneurons in the ventrolateral motor nuclei. They give rise to ventral and dorsal dendrite groups which have extensive arborization areas. A dorsolateral cell group in the rostral three quarters of the oculomotorius nucleus innervates ipsilateral eye muscles (m.obl.inf., m.rect.inf., m.rect.med.) and a ventromedial cell group innervates the contralateral m. rectus superior. Ipsilateral axons originate from ventral dendrites, contralateral axons emerge from the medial aspect of cell bodies, or from dorsal dendrites, and form a "knee" as they turn around the nucleus on their way to join the ipsilateral axons. A few labeled small cells found dorsal and lateral to the main nucleus in the central gray matter are regarded as representing the nucleus of Edinger-Westphal. The trochlearis nucleus is continuous with the ventromedial cell group of the oculomotorius nucleus. The axons originate in dorsal dendrites, run dorsally along the border of the gray matter and pierce the velum medullare on the contralateral side. A compact dendritic bundle of oculomotorius neurons traverse the nucleus, and side branches appear to be in close apposition to the trochlearis neurons. A dorsomedial and a ventrolateral cell group becomes labeled via the abducens nerve. The former supplies the m. rectus lateralis, while the latter corresponds to the accessorius abducens nucleus which innervates the mm. rectractores. Neurons in this latter nucleus are large and multipolar, resembling the neurons in the ventrolateral motor nuclei. Their axons originate from dorsal dendrites and form a "knee" around the dorsomedial aspect of the abducens nucleus. Cobalt applied to the hypoglossus nerve reaches a dorsomedial cell group (the nucleus proper), spinal motoneurons and sympathetic preganglionic neurons. Of the dorsomedial motor cells, the hypoglossus neurons are the largest, and a branch of their ventral dendrites terminates on the contralateral side. Some functional and developmental biological aspects of the morphological findings, such as the crossing axons and the peculiar morphology of the accessory abducens nucleus, are discussed.     

A QUANTITATIVE STUDY OF SYNAPSES ON MOTOR NEURON DENDRITIC GROWTH CONES IN DEVELOPING MOUSE SPINAL CORD

The proportion of synaptic contacts occurring on dendrites as well as on dendritic growth cones and filopodia was determined from electron micrographs of developing mouse (C57BL/6J) spinal cord. Comparable areas of the marginal zone adjacent to the lateral motor nucleus were sampled from specimens on the 13th–16th days of embryonic development (E13–E16). At the beginning of this period, synapses upon growth cones and filopodia comprise about 80% of the observed synaptic junctions, but this proportion decreases with developmental time so that in E16 specimens growth cone synapses account for slightly less than 30% of the synaptic population. Conversely, at E13, synapses upon dendrites comprise less than 20% of the total number of synapses, but increase with developmental time so that they account for about 65% of the synaptic population of E16 specimens. From these data, we suggest the following temporal sequence for the formation of synaptic junctions on motor neuron dendrites growing into the marginal zone. New synapses are initially made upon the filopodia of dendritic growth cones. A synaptically contacted filopodium expands to become a growth cone while the original growth cone begins to differentiate into a dendrite. This process is repeated as the dendrite grows farther into the marginal zone so that synapses originally made with filopodia come to be located upon dendrites. This speculation is briefly discussed in relation to the work and ideas of others concerning synaptogenesis and dendritic development.     

Peculiarities of structural-functional organization of the motor neuropil in the dragonfly thoracic ganglia

The study considers structural-functional relations in motor neuropil of the thoracic ganglia in dragonflies-insects capable of performing very complex and fast maneuvering in flight. The motor neuropil in dragonflies was shown to be more differentiated than in less mobile insects, while its motor nuclei are more outlined and approached to each other. There were revealed dendrites of the leg muscle motoneurons (intermediate nucleus), running to the anterior and posterior nuclei that contain dendrites of the wing muscle motoneurons. A possible role of such a dendrite approaching is discussed for close functional cooperation of wing and leg muscles essential for dragonflies to catch a large prey in flight by using their legs. Peculiarities of structural organization of the wing muscle motoneurons in dragonflies and locusts are considered to suggest the greater functional capabilities of motoneurons in the dragonfly motor apparatus.     

Lobula plate and ocellar interneurons converge onto a cluster of descending neurons leading to neck and leg motor neuropil in Calliphora erythrocephala

Summary In the fly, Calliphora erythrocephala, a cluster of three Y-shaped descending neurons (DNOVS 1–3) receives ocellar interneuron and vertical cell (VS4–9) terminals. Synaptic connections to one of them (DNOVS 1) are described. In addition, three types of small lobula plate vertical cell (sVS) and one type of contralateral horizontal neuron (Hc) terminate at DNOVS 1, as do two forms of ascending neurons derived from thoracic ganglia. A contralateral neuron, with terminals in the opposite lobula plate, arises at the DNOVS cluster and is thought to provide heterolateral interaction between the VS4–9 output of one side to the VS4–9 dendrites of the other. DNOVS 2 and 3 extend through pro-, meso-, and metathoracic ganglia, branching ipsilaterally within their tract and into the inner margin of leg motor neuropil of each ganglion. DNOVS 1 terminates as a stubby ending in the dorsal prothoracic ganglion onto the main dendritic trunks of neck muscle motor neurons. Convergence of VS and ocellar interneurons to DNOVS 1 comprises a second pathway from the visual system to the neck motor, the other being carried by motor neurons arising in the brain. Their significance for saccadic head movement and the stabilization of the retinal image is discussed.     

Motor control of the mandible closer muscle in ants

Despite their simple design, ant mandible movements cover a wide range of forces, velocities and amplitudes. The mandible is controlled by the mandible closer muscle, which is composed of two functionally distinct subpopulations of muscle fiber types: fast fibers (short sarcomeres) and slow ones (long sarcomeres). The entire muscle is controlled by 10-12 motor neurons, 4-5 of which exclusively supply fast muscle fibers. Slow muscle fibers comprise a posterior and an antero-lateral group, each of which is controlled by 1-2 motor neurons. In addition, 3-4 motor neurons control all muscle fibers together. Simultaneous recordings of muscle activity and mandible movement reveal that fast movements require rapid contractions of fast muscle fibers. Slow and subtle movements result from the activation of slow muscle fibers. Forceful movements are generated by simultaneous co-activation of all muscle fiber types. Retrograde tracing shows that most dendritic arborizations of the different sets of motor neurons share the same neuropil in the subesophageal ganglion. In addition, fast motor neurons and neurons supplying the lateral group of slow closer muscle fibers each invade specific parts of the neuropil that is not shared by the other motor neuron groups. Some bilateral overlap between the dendrites of left and right motor neurons exists, particularly in fast motor neurons. The results explain how a single muscle is able to control the different movement parameters required for the proper function of ant mandibles.     

Glycinergic transmission regulates dendrite size in organotypic culture

We previously demonstrated that inhibitory synaptic transmission influences dendrite development in vivo. We now report an analogous finding in an organotypic culture of a glycinergic projection nucleus, the medial nucleus of the trapezoid body (MNTB), and its postsynaptic target, the lateral superior olive (LSO) of gerbils. Cultures were generated at 6–7 days postnatal and grown in serum containing medium with or without the glycine receptor antagonist, strychnine (SN), at 2 μM. LSO neurons were then labeled with biocytin, and the dendritic arbors were analyzed morphometrically. Compared to neurons from age-matched in vivo tissue, the neurons cultured in control media were somewhat atrophic, including decreases in dendritic branching and length. Incubation in strychnine led to a dramatic increase in dendritic branching and total dendritic length. Control neurons averaged 6.3 branches, compared to 18 branches/neuron in SN-treated cultures. There was a similar increase in primary dendrites and total dendritic length. The physical elimination of MNTB cells did not mimic SN treatment, presumably because glycinergic LSO neurons generated intrinsic connections. In fact, the LSO soma area was significantly greater following MNTB removal, suggesting that these afferents provide a second signal to postsynaptic neurons. These results suggest that spontaneous glycinergic transmission regulates the growth of postsynaptic processes. © 1996 John Wiley & Sons, Inc.     

Effect of auditory deafferentation on the synaptic connectivity of a pair of identified interneurons in adult field crickets

In adult crickets, Teleogryllus oceanicus, unilateral auditory deafferentation causes the medial dendrites of an afferent-deprived, identified auditory interneuron (Int-1) in the prothoracic ganglion to sprout and form new functional connections in the contralateral auditory neuropil. The establishment of these new functional connections by the deafferented Int-1, however, does not appear to affect the physiological responses of Int-1's homolog on the intact side of the prothoracic ganglion which also innervates this auditory neuropil. Thus it appears that the sprouting dendrites of the deafferented Int-1 are not functionally competing with those of the intact Int-1 for synaptic connections in the remaining auditory neuropil following unilateral deafferentation in adult crickets. Moreover, we demonstrate that auditory function is restored to the afferent-deprived Int-1 within 4-6 days following deafferentation, when few branches of Int-1's medial dendrites can be seen to have sprouted. The strength of the physiological responses and extent of dendritic sprouting in the deafferented Int-1 progressively increase with time following deafferentation. By 28 days following deafferentation, most of the normal physiological responses of Int-1 to auditory stimuli have been restored in the deafferented Int-1, and the medial dendrites of the deafferented Int-1 have clearly sprouted and grown across into the contralateral auditory afferent field. The strength of the physiological responses of the deafferented Int-1 to auditory stimuli and extent of dendritic sprouting in the deafferented Int-1 are greater in crickets deafferented as juveniles than as adults. Thus, neuronal plasticity persists in Int-1 following sensory deprivation from the earliest juvenile stages through adulthood.     

A pair of descending neurons with dendrites in the optic lobes projecting directly to thoracic ganglia of dipterous insects

Summary The lobula descending neuron (LDN) of dipterous insects is a unique nerve cell (one on each side of the brain) that projects directly from the lobula complex of the optic lobes to neuropil in thoracic ganglia. In the supraoesophageal ganglia the LDN has two prominent groups of branches of which at least one is dendritic in nature. Postsynaptic branches are distributed in the lobula and some branches, the synaptic relations of which are not yet known, extend to the lobula plate. A second group of branches is found among dendrites of the descending neurons proper, in the lateral midbrain.The arborizations of LDN in the lobula (and lobula plate) map onto a retinotopic neuropil region subserving a posterior strip of the visual field of the compound eye. The arborizations in the lobula complex are extremely variable in size. The numbers of dendritic spines they possess vary greatly between left and right optic lobes of one animal, and between individual animals.     

Dendritic morphology is altered in hippocampal neurons following prenatal compromise

Chronic placental insufficiency (CPI), a known cause of intrauterine growth restriction, can lead to structural alterations in the developing brain that might underlie postnatal neurological deficits. We have previously demonstrated significant reductions in the volumes of hippocampal neuropil layers in fetal guinea pig brains following experimentally induced growth restriction. To determine the components of the neuropil affected in the brains of growth restricted (GR) fetuses, the dendritic morphology of CA1 pyramidal neurons and dentate granule cells was examined. CPI was induced by unilateral uterine artery ligation in pregnant guinea pigs at midgestation (term approximately 67 days). Hippocampi from control and GR fetuses were stained using the Rapid Golgi technique and the growth and branching of the dendritic arbors were quantified using the Sholl method. In addition, the density of dendritic spines was determined on the apical arbors of each population. In GR brains (n = 7) compared to controls (n = 7), there was a reduction in dendritic elongation (p < 0.005) and an alteration in the branch point distribution in CA1 basal arbors, and a reduction both in the outgrowth (p < 0.05) and branch point number (p < 0.05) of CA1 apical arbors. Dentate granule cells from GR brains also demonstrated reduced dendritic outgrowth (p < 0.05). There was an increase in dendritic spine density in both neuronal populations; this might be due either to altered synaptic pruning or as a compensatory mechanism for reduced dendritic length. These findings demonstrate that a chronic prenatal insult causes selective changes in the morphology of hippocampal cell dendrites and may lead to alterations in hippocampal function in the postnatal period.     

Medullary neurons in the core white matter of the olfactory bulb: a new cell type

The structure of a new cell type, termed the medullary neuron (MN) because of its intimate association with the rostral migratory stream (RMS) in the bulbar core, is described in the adult rat olfactory bulb. The MN is a triangular or polygonal interneuron whose soma lies between the cellular clusters of the RMS or, less frequently, among the neuron progenitors therein. MNs are easily distinguished from adjacent cells by their large size and differentiated structure. Two MN subtypes have been categorized by the Golgi technique: spiny pyramidal neurons and aspiny neurons. Both MN subtypes bear a large dendritic field impinged upon by axons in the core bulbar white matter. A set of collaterals from the adjacent axons appears to terminate on the MN dendrites. The MN axon passes in close apposition to adjacent neuron progenitors in the RMS. MNs are immunoreactive with antisera raised against gamma-aminobutyric acid and glutamate decarboxylase 65/67. Electron-microscopic observations confirm that MNs correspond to fully differentiated, mature neurons. MNs seem to be highly conserved among macrosmatic species as they occur in Nissl-stained brain sections from mouse, guinea pig, and hedgehog. Although the functional role of MNs remains to be determined, we suggest that MNs represent a cellular interface between endogenous olfactory activity and the differentiation of new neurons generated during adulthood.     

Sex differences in the motor nucleus of cranial nerve IX-X in Xenopus laevis: a quantitative Golgi study

In the clawed frog (Xenopus laevis), motor neurons in cranial nerve nucleus IX-X control contraction of laryngeal muscles responsible for sexually dimorphic vocal behaviors. We examined sex differences in dendritic arbors of n.IX-X cells using the Golgi-Cox method. Three morphological classes of somal types (ovoid, triangular, and elongate) are present in similar frequencies in n.IX-X of both males and females. The male n.IX-X neuron is a more complex and hypertrophied version of the female n.IX-X cell. The number of primary dendrites is the same for both sexes, but males have more total dendritic segments. The overall dendritic length of male n.IX-X neurons is two to three times that of the female. Males have longer dendritic segments between all branch points. Male and female frogs differ in levels of circulating androgens; neurons of n.IX-X are targets for androgenic steroids. To determine if androgen can affect dendritic morphology in adult females, we examined Golgi-impregnated cells in n.IX-X from ovariectomized females treated with testosterone for 1 month. The total number of dendritic segments was reduced by androgen treatment due to reduction in the number of higher order dendritic segments; the number of primary dendritic segments was unchanged. Androgen treatment may induce resorption of higher order dendritic branches. The overall dendritic length of androgen-treated female n.IX-X neurons was unchanged, and dendritic segments were longer. Thus, although androgen can alter dendrites of n.IX-X cells in adult females, this short-term treatment does not produce a masculine dendritic architecture.     

Abnormal medial prefrontal cortex connectivity and defective fear extinction in the presymptomatic G93A SOD1 mouse model of ALS

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neuropathy associated with the degeneration of spinal and brainstem motor neurons. Although ALS is essentially considered as a lower motor neuron disease, prefrontal cortex atrophy underlying executive function deficits have been extensively reported in ALS patients. Here, we examine whether prefrontal cortex neuronal abnormalities and related cognitive impairments are present in presymptomatic G93A Cu/Zn superoxide dismutase mice, a mouse model for familial ALS. Structural characteristics of prelimbic/infralimbic (PL/IL) medial prefrontal cortex (mPFC) neurons were studied in 3-month-old G93A and wild-type mice with the Golgi–Cox method, while mPFC-related cognitive operations were assessed using the conditioned fear extinction paradigm. Sholl analysis performed on the dendritic material showed a reduction in dendrite length and branch nodes on basal dendrites of PL/IL neurons in G93A mice. Spine density was also decreased on basal dendrite segments of branch order five. Consistent with the altered morphology of PL/IL cortical regions, G93A mice showed impaired extinction of conditioned fear. Our findings indicate that abnormal prefrontal cortex connectivity and function are appreciable before the onset of motor disturbances in this model.