Medial Dendrites Research Articles

Modification of temporal pattern sensitivity for inputs from medial entorhinal cortex by lateral inputs in hippocampal granule cells.

The medial dendrites (MDs) of granule cells (GCs) receive spatial information through the medial entorhinal cortex (MEC) from the entorhinal cortex in the rat hippocampus while the distal dendrites (DDs) of GCs receive non-spatial information (sensory inputs) through the lateral entorhinal cortex (LEC). However, it is unclear how information processing through the two pathways is managed in GCs. In this study, we investigated associative information processing between two independent inputs to MDs and DDs. First, in physiological experiments, to compare response characteristics between MDs and DDs, electrical stimuli comprising five pulses were applied to the MPP or LPP in rat hippocampal slices. These stimuli transiently decreased the excitatory postsynaptic potentials (EPSPs) of successive input pulses to MDs, whereas EPSPs to DDs showed sustained responses. Next, in computational experiments using a local network model obtained by fitting of the physiological experimental data, we compared associative information processing between DDs and MDs. The results showed that the temporal pattern sensitivity for burst inputs to MDs depended on the frequency of the random pulse inputs applied to DDs. On the other hand, with lateral inhibition to GCs from interneurons, the temporal pattern sensitivity for burst inputs to MDs was enhanced or tuned up according to the frequency of the random pulse inputs to the other cells. Thus, our results suggest that the temporal pattern sensitivity of spatial information depends on the non-spatial inputs to GCs.

The use of L-dopa induces the resistance of Mauthner neurons to the neurotoxic action of beta-amyloid

BACKGROUND: Mauthner goldfish (Carassius auratus (L)) cells serve as model objects for studying brain pathologies at the level of identified neurons and their individual dendrites. L-dopa may be an agent that decelerates the destruction of neurons caused by the toxic effects of beta-amyloid.
 AIMS: To study the three-dimensional structure of Mauthner neurons in goldfish and the ultrastructure of their afferent synapses under the influence of L-dopa and the toxic 2535 fragment of beta-amyloid.
 MATERIAL AND METHODS: This study was performed on the Mauthner neurons of goldfish fry (n=12) by using light and electron microscopy. Serial sections 3 m thick were used to identify and integrally reconstruct the structure of Mauthner neurons; determine the volume of the soma and ventral and lateral dendrites; and study the structure of afferent synapses.
 RESULTS: The use of L-dopa stabilized the size of the soma and ventral dendrites. The reduction in the volume of lateral dendrites was accompanied either by an increase in the volume of their branches under the action of beta-amyloid followed by that of L-dopa or by an increase in the volume of medial dendrites under the action of L-dopa followed by that of beta-amyloid. Although pathological changes in the ultrastructure of neurons and afferent synapses were not found, signs of early amyloidosis were detected.
 CONCLUSION: The use of L-dopa decelerates the degeneration of Mauthner neurons. The resistance of whole neurons to the neurotoxic action of beta-amyloid has been suggested to be due to the mechanism of structural homeostasis aiming at the compensatory restoration of the morphological organization of neurons.

Dendritic Kv4.2 potassium channels selectively mediate spatial pattern separation in the dentate gyrus

SummaryThe capacity to distinguish comparable experiences is fundamental for the recall of similar memories and has been proposed to require pattern separation in the dentate gyrus (DG). However, the cellular mechanisms by which mature granule cells (GCs) of the DG accomplish this function are poorly characterized. Here, we show that Kv4.2 channels selectively modulate the excitability of medial dendrites of dentate GCs. These dendrites are targeted by the medial entorhinal cortex, the main source of spatial inputs to the DG. Accordingly, we found that the spatial pattern separation capability of animals lacking the Kv4.2 channel is significantly impaired. This points to the role of intrinsic excitability in supporting the mnemonic function of the dentate and to the Kv4.2 channel as a candidate substrate promoting spatial pattern separation.

Compensatory Changes in Mauthner Neurons in Goldfish Induced by Sensory Stimulation and Application of β-Amyloid

Objectives. To study the structure and formation of Mauthner neuron dendrites in goldfish exposed to neurotoxic β-amyloid fragment 25–35 and prolonged sensory stimulation influencing the afferent inputs to these neurons. Materials and methods. Goldfish Mauthner neurons were studied by light and electron microscopy. Individual dendrites were identified, their volumes were determined, and synapse structure was assessed using virtual 3D images of Mauthner neurons obtained from serial sections of thickness 3 μm. The functional status of Mauthner neurons was evaluated indirectly from the motor lateralization of the fish. Results. Mauthner neurons responded to application of β-amyloid combined with subsequent prolonged sensory stimulation with decreases in the volume of the ventral dendrites, damage to their ultrastructure, and degeneration of a proportion of synapses. Degeneration of more active neurons was more significant than that of less active cells. Newly formed medial dendrites had greater volume and less damaged synapse ultrastructure than ventral dendrites. There were no differences in the sizes of specialized junctions between synapses of the same type on ventral and medial synapses. Conclusions. Medial dendrite formation is a compensatory reaction to dystrophy of the ventral dendrite due to the experimental treatment.

Regulation of subcellular dendritic synapse specificity by axon guidance cues.

Neural circuit assembly occurs with subcellular precision, yet the mechanisms underlying this precision remain largely unknown. Subcellular synaptic specificity could be achieved by molecularly distinct subcellular domains that locally regulate synapse formation, or by axon guidance cues restricting access to one of several acceptable targets. We address these models using two Drosophila neurons: the dbd sensory neuron and the A08a interneuron. In wild-type larvae, dbd synapses with the A08a medial dendrite but not the A08a lateral dendrite. dbd-specific overexpression of the guidance receptors Unc-5 or Robo-2 results in lateralization of the dbd axon, which forms anatomical and functional monosynaptic connections with the A08a lateral dendrite. We conclude that axon guidance cues, not molecularly distinct dendritic arbors, are a major determinant of dbd-A08a subcellular synapse specificity.

Shaking-B misexpression increases the formation of gap junctions but not chemical synapses between auditory sensory neurons and the giant fiber of Drosophila melanogaster.

The synapse between auditory Johnston’s Organ neurons (JONs) and the giant fiber (GF) of Drosophila is structurally mixed, being composed of cholinergic chemical synapses and Neurobiotin- (NB) permeable gap junctions, which consist of the innexin Shaking-B (ShakB). Previous observations showed that misexpression of one ShakB isoform, ShakB(N+16), in a subset of JONs that do not normally form gap junctions results in their de novo dye coupling to the GF. Misexpression of the transcription factor Engrailed (En) in these neurons also has this effect, and in addition causes the formation of new chemical synapses. These results, along with earlier studies suggesting that gap junctions are required for the development of some chemical synapses, led to the hypothesis that ShakB would, like En, have an instructive effect on the distribution of mixed chemical/electrical contacts. To test this, we first confirmed quantitatively that ShakB(N+16) misexpression increased the dye-coupling of JONs with the GF, indicating the formation of ectopic gap junctions. Conversely, expression of the ‘incorrect’ isoform, ShakB(N), abolished dye coupling. Immunocytochemistry of the ShakB protein showed that ShakB(N+16) increased gap junctional plaques in JON axons but ShakB(N) did not. To test our hypothesis, fluorescently-labeled presynaptic active zone protein (Brp) was expressed in JONs and the changes in its distribution on the GF dendrites was assayed with confocal microscopy in animals with misexpression of ShakB(N+16), ShakB(N) or, as a positive control, En. Using different methods of image analysis, we confirmed our previous result that En misexpression increased the chemical synapses with the GF and the amount of GF medial dendrite branching. However, contrary to our hypothesis, misexpression of ShakB did not increase these parameters. Immunostaining showed no association between presynaptic active zones and the new ShakB plaques, further evidence against the hypothesis. We conclude that both subsets of JON form chemical synapses onto the GF dendrites but only one population forms gap junctions, comprised of ShakB(N+16). Misexpression of this isoform in all JONs does not instruct the formation of new mixed chemical/electrical synapses, but results in the insertion of new gap junctions, presumably at the sites of existing chemical synaptic contacts with the GF.

Distribution and density of contacts from noradrenergic and serotonergic boutons on the dendrites of neck flexor motoneurons in the adult cat.

Serotonergic (5-HT) and noradrenergic (NA) input to spinal motoneurons is essential for generating plateau potentials and self-sustained discharges. Extensor motoneurons are densely innervated by 5-HT and NA synapses and have robust plateau potentials and self-sustained discharges. Conversely, plateau potentials and self-sustained discharges are very rare in flexor motoneurons. The most likely reasons for this difference are that flexor motoneurons have few 5-HT and NA synapses and/or they are distributed distant to the channels responsible for plateau potentials and self-sustained discharges. However, the distribution of 5-HT and NA synapses on flexor motoneurons is unknown. Here we describe the distribution and density of 5-HT and NA synapses on motoneurons that innervate the flexor neck muscle, rectus capitis anterior (RCA), in the adult cat. Using a combination of intracellular staining, fluorescent immunohistochemistry, and 3D reconstruction techniques, we found that 5-HT and NA synapses are widely distributed throughout the dendritic trees of RCA motoneurons, albeit with a strong bias to small-diameter dendrites and to medial dendrites in the case of NA contacts. The number of 5-HT and NA contacts per motoneuron ranged, respectively, from 381 to 1,430 and from 642 to 1,382, which is 2.3- and 1.4-fold less than neck extensor motoneurons (Montague et al., J Comp Neurol 2013;521:638-656). These results suggest that 5-HT and NA synapses on flexor motoneurons may provide a powerful means of amplifying synaptic currents without incurring plateau potentials or self-sustained discharges. This feature is well suited to meet the biomechanical demands imposed on flexor muscles during different motor tasks.

Spatial information enhanced by non-spatial information in hippocampal granule cells.

The hippocampus organizes sequential memory composed of non-spatial information (such as objects and odors) and spatial information (places). The dentate gyrus (DG) in the hippocampus receives two types of information from the lateral and medial entorhinal cortices. Non-spatial and spatial information is delivered respectively to distal and medial dendrites (MDs) of granule cells (GCs) within the molecular layer in the DG. To investigate the role of the association of those two inputs, we measured the response characteristics of distal and MDs of a GC in a rat hippocampal slice and developed a multi-compartment GC model with dynamic synapses; this model reproduces the response characteristics of the dendrites. Upon applying random inputs or input sequences generated by a Markov process to the computational model, it was found that a high-frequency random pulse input to distal dendrites (DDs) and, separately, regular burst inputs to MDs were effective for inducing GC activation. Furthermore, when the random and theta burst inputs were simultaneously applied to the respective dendrites, the pattern discrimination for theta burst input to MDs that caused slight GC activation was enhanced in the presence of random input to DDs. These results suggest that the temporal pattern discrimination of spatial information is originally involved in a synaptic characteristic in GCs and is enhanced by non-spatial information input to DDs. Consequently, the co-activation of two separate inputs may play a crucial role in the information processing on dendrites of GCs by usefully combing each temporal sequence.

Morphofunctional and Ultrastructural Consequences of Application of Beta-Amyloid on Goldfish Mauthner Neurons

We studied the correlation between functional activity and 3D structure of Mauthner neurons (MNs) of the goldfish in the norm, after isolated application of an aggregated fragment of beta-amyloid 25-35 (Aβ25-35), and a combination of such application with optokinetic stimulation of the fish. It was shown that the clear correlation between the structure and function of MNs observed in the control is strongly disturbed after the action of beta-amyloid aggregates. According to the data of ultrastructural analysis, destruction of the cytoskeleton, vacuolization of the MN cytoplasm, and depletion of the vesicular apparatus of afferent synapses are the main events responsible for such effect of Aβ25-35. Fatiguing sensory optokinetic stimulation of fishes applied against the background of action of Aβ25-35 induces dystrophy of the ventral MN dendrites and the formation, near the latter, of earlier absent hypertrophied medial dendrites; these dendrites were comparable in their dimension with the main MN dendrites in control fishes. The data obtained allow us to suppose that a traumatic mechanical influence of the beta-amyloid aggregates on neurons and their processes is an important factor in the development of amyloidosis-related neurodegenerative diseases, and destruction of the cytoskeleton is one of the key phenomena from this aspect.

Macrocircuits for Sound Localization Use Leaky Coincidence Detectors and Specialized Synapses

The auditory system computes sound location by detecting submillisecond time differences in the arrival of sound at the two ears. Studies by van der Heijden etal. (2013) and Roberts etal. (2013) in this issue of Neuron shed light on how this is accomplished by the interaction of excitatory and inhibitory synapses.

Electrophysiological recordings from the giant fiber pathway of D. melanogaster.

When startled adult D. melanogaster react by jumping into the air and flying away. In many invertebrate species, including D. melanogaster, the "escape" (or "startle") response during the adult stage is mediated by the multi-component neuronal circuit called the Giant Fiber System (GFS). The comparative large size of the neurons, their distinctive morphology and simple connectivity make the GFS an attractive model system for studying neuronal circuitry. The GFS pathway is composed of two bilaterally symmetrical Giant Fiber (GF) interneurons whose axons descend from the brain along the midline into the thoracic ganglion via the cervical connective. In the mesothoracic neuromere (T2) of the ventral ganglia the GFs form electro-chemical synapses with 1) the large medial dendrite of the ipsilateral motorneuron (TTMn) which drives the tergotrochanteral muscle (TTM), the main extensor for the mesothoracic femur/leg, and 2) the contralateral peripherally synapsing interneuron (PSI) which in turn forms chemical (cholinergic) synapses with the motorneurons (DLMns) of the dorsal longitudinal muscles (DLMs), the wing depressors. The neuronal pathway(s) to the dorsovental muscles (DVMs), the wing elevators, has not yet been worked out (the DLMs and DVMs are known jointly as indirect flight muscles - they are not attached directly to the wings, but rather move the wings indirectly by distorting the nearby thoracic cuticle) (King and Wyman, 1980; Allen et al., 2006). The di-synaptic activation of the DLMs (via PSI) causes a small but important delay in the timing of the contraction of these muscles relative to the monosynaptic activation of TTM (~0.5 ms) allowing the TTMs to first extend the femur and propel the fly off the ground. The TTMs simultaneously stretch-activate the DLMs which in turn mutually stretch-activate the DVMs for the duration of the flight. The GF pathway can be activated either indirectly by applying a sensory (e.g."air-puff" or "lights-off") stimulus, or directly by a supra-threshold electrical stimulus to the brain (described here). In both cases, an action potential reaches the TTMs and DLMs solely via the GFs, PSIs, and TTM/DLM motoneurons, although the TTMns and DLMns do have other, as yet unidentified, sensory inputs. Measuring "latency response" (the time between the stimulation and muscle depolarization) and the "following to high frequency stimulation" (the number of successful responses to a certain number of high frequency stimuli) provides a way to reproducibly and quantitatively assess the functional status of the GFS components, including both central synapses (GF-TTMn, GF-PSI, PSI-DLMn) and the chemical (glutamatergic) neuromuscular junctions (TTMn-TTM and DLMn-DLM). It has been used to identify genes involved in central synapse formation and to assess CNS function.

Electrophysiological Recordings from the Giant Fiber Pathway of <em>D. melanogaster</em>

When startled adult D. melanogaster react by jumping into the air and flying away. In many invertebrate species, including D. melanogaster, the "escape" (or "startle") response during the adult stage is mediated by the multi-component neuronal circuit called the Giant Fiber System (GFS). The comparative large size of the neurons, their distinctive morphology and simple connectivity make the GFS an attractive model system for studying neuronal circuitry. The GFS pathway is composed of two bilaterally symmetrical Giant Fiber (GF) interneurons whose axons descend from the brain along the midline into the thoracic ganglion via the cervical connective. In the mesothoracic neuromere (T2) of the ventral ganglia the GFs form electro-chemical synapses with 1) the large medial dendrite of the ipsilateral motorneuron (TTMn) which drives the tergotrochanteral muscle (TTM), the main extensor for the mesothoracic femur/leg, and 2) the contralateral peripherally synapsing interneuron (PSI) which in turn forms chemical (cholinergic) synapses with the motorneurons (DLMns) of the dorsal longitudinal muscles (DLMs), the wing depressors. The neuronal pathway(s) to the dorsovental muscles (DVMs), the wing elevators, has not yet been worked out (the DLMs and DVMs are known jointly as indirect flight muscles - they are not attached directly to the wings, but rather move the wings indirectly by distorting the nearby thoracic cuticle) (King and Wyman, 1980; Allen et al., 2006). The di-synaptic activation of the DLMs (via PSI) causes a small but important delay in the timing of the contraction of these muscles relative to the monosynaptic activation of TTM (~0.5 ms) allowing the TTMs to first extend the femur and propel the fly off the ground. The TTMs simultaneously stretch-activate the DLMs which in turn mutually stretch-activate the DVMs for the duration of the flight. The GF pathway can be activated either indirectly by applying a sensory (e.g."air-puff" or "lights-off") stimulus, or directly by a supra-threshold electrical stimulus to the brain (described here). In both cases, an action potential reaches the TTMs and DLMs solely via the GFs, PSIs, and TTM/DLM motoneurons, although the TTMns and DLMns do have other, as yet unidentified, sensory inputs. Measuring "latency response" (the time between the stimulation and muscle depolarization) and the "following to high frequency stimulation" (the number of successful responses to a certain number of high frequency stimuli) provides a way to reproducibly and quantitatively assess the functional status of the GFS components, including both central synapses (GF-TTMn, GF-PSI, PSI-DLMn) and the chemical (glutamatergic) neuromuscular junctions (TTMn-TTM and DLMn-DLM). It has been used to identify genes involved in central synapse formation and to assess CNS function.

Distribution of vestibulospinal contacts on the dendrites of ipsilateral splenius motoneurons: An anatomical substrate for push-pull interactions during vestibulocollic reflexes

Excitatory and inhibitory synapses may control neuronal output through a push-pull mechanism—that is, increases in excitation are coupled to simultaneous decreases in inhibition or vice versa. This pattern of activity is characteristic of excitatory and inhibitory vestibulospinal axons that mediate vestibulocollic reflexes. Previously, we showed that medial vestibulospinal tract (MVST) neurons in the rostral descending vestibular nucleus (DVN), an excitatory pathway, primarily innervate the medial dendrites of contralateral splenius motoneurons. In the present study, we tested the hypothesis that the counterparts of the push-pull mechanism, the ipsilateral inhibitory MVST synapses, are distributed on the dendritic tree such that the interactions with excitatory MVST synapses are enhanced. We combined anterograde tracing and intracellular staining in adult felines and show that most contacts (∼ 70%) between inhibitory MVST neurons in the rostral DVN and ipsilateral splenius motoneurons are also located on medial dendrites. There was a weak bias towards proximal dendrites. Using computational methods, we further show that the organization of excitatory and inhibitory MVST synapses on splenius motoneurons increases their likelihood for interaction. We found that if either excitatory or inhibitory MVST synapses were uniformly distributed throughout the dendritic tree, the proportion of inhibitory contacts in close proximity to excitatory contacts decreased. Thus, the compartmentalized distribution of excitatory and inhibitory MVST synapses on splenius motoneurons may be specifically designed to enhance their interactions during vestibulocollic reflexes. This suggests that the push-pull modulation of motoneuron output is based, in part, on the spatial arrangement of synapses on the dendritic tree.

Effect of localized innervation of the dendritic trees of feline motoneurons on the amplification of synaptic input: a computational study

Previous studies show that the activation of voltage-dependent channels is dependent on the local density of synapses in the dendritic region containing voltage-dependent channels. We hypothesized that the selective innervation of excitatory vestibulospinal (VST) neurons on the medial dendrites of contralateral splenius motoneurons is designed to enhance the activation of persistent inward currents (PICs) mediated by dendritic L-type Ca(2+) channels. Using compartmental models of splenius motoneurons we compared the synaptic current reaching the soma in response to excitatory input generated by synapses with two different distribution patterns. The medial distribution was based on the arrangement of VST synapses on the dendrites of contralateral splenius motoneurons and the uniform distribution was based on an arrangement of synapses with no particular bias to any region of the dendritic tree. The number of synapses in each distribution was designed to match estimates of the number of VST synapses activated by head movements. In the absence of PICs, the current delivered by the synapses in the uniform distribution was slightly greater. However, the maximal currents were small, < or = 4.1 nA, regardless of the distribution of synapses. In models equipped with L-type Ca(2+) channels, PIC activation was largely determined by the local density of synapses in proximity to the L-type Ca(2+) channels. In 3 of 5 cells, this led to a 2- to 4-fold increase in the current generated by synapses in the medial distribution compared to the uniform distribution. In the other two cells, the amplification bias was in favour of the medial distribution but was either small or restricted to a narrow range of frequencies. These simulations suggest that the innervation pattern of VST axons on contralateral splenius motoneurons is arranged to strengthen an otherwise weak synaptic input by increasing the likelihood of activating PICs. Additional simulations suggest that this prediction can be tested using common experimental protocols.

Effects of Behavioral Depression and Chronic Influence of Antidepressants on NMDA/Glutamate Receptor-Mediated Responses of Neurons of the Rat Gyrus Dentatus

In studies on superfused slices obtained from the rat hippocampus, we extracellularly recorded field EPSP (fEPSPs), pharmacologically isolated components of these fEPSP, which were related to activation of synaptic NMDA-glutamate receptors, and neuronal responses of the dentate gyrus, which were mediated by activation of extrasynaptic NMDA-glutamate receptors. Recordings were performed in junctions formed by fibers of the medial perforant pathway and dendrites of granular cells of the gyrus dentatus. In the course of the development of behavioral depression in rats, which was caused by zoosocial isolation or chronic injection of dexamethasone, the amplitude of fEPSPs decreased, on average, by 19.8 and 26.0%, respectively, while the NMDA components of fEPSP increased by 28.6 and 33.4%; the rise in the amplitude of neuronal responses recorded in the gyrus dentatus, which were mediated by the activation of extrasynaptic NMDA receptors (by 75.4 and 92.3%), was clearly expressed. In intact rats, chronic (over 14 days) injections of tricyclic antidepressants, imipramine and amitriptyline, as well as of an atypical antidepressant, maprotiline, resulted in an increase in the fEPSP amplitude by 22.1 to 25.9%. At the same time, the amplitude of NMDA components of fEPSP dropped by 27.0 to 29.1%, while the amplitude of responses mediated by the activation of extrasynaptic NMDA-glutamate receptors decreased by 46.1 to 49.8%. Changes in the neuronal responses in the gyrus dentatus, which were mediated by the activation of NMDA-glutamate receptors, are related to an increase or decrease in the number of such receptors. It is supposed that an increase in the total number of NMDA-glutamate receptors under conditions of behavioral depression results in a deterioration of the energy supply of cerebral neurons, while an increase in the extrasynaptic pool of NMDA-glutamate receptors leads to suppression of biosynthesis of neurotrophins and to injury of neurons. As a general result, informational processes in the brain are subjected to significant negative influences. Chronic injections of antidepressants promote a permanent rise in the concentration of noradrenaline and serotonin in extracellular environments and the activation of monoamine receptors positively conjugated with adenylate cyclase; suppression of expression of informational RNAs, which encode subunits of NMDA-glutamate receptors, and a decrease in the number of these receptors. These events improve the functional state of neurons.

Synaptic and morphological characteristics of temperature-sensitive and -insensitive rat hypothalamic neurones.

1. Intracellular recordings were made from neurones in rat hypothalamic tissue slices, primarily in the preoptic area and anterior hypothalamus, a thermoregulatory region that integrates central and peripheral thermal information. The present study compared morphologies and local synaptic inputs of warm-sensitive and temperature-insensitive neurones. 2. Warm-sensitive neurones oriented their dendrites perpendicular to the third ventricle, with medial dendrites directed toward the periventricular region and lateral dendrites directed toward the medial forebrain bundle. In contrast, temperature-insensitive neurones generally oriented their dendrites parallel to the third ventricle. 3. Both warm-sensitive and temperature-insensitive neurones displayed excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). In most cases, EPSP and IPSP frequencies were not affected by temperature changes, suggesting that temperature-insensitive neurones are responsible for most local synapses within this hypothalamic network. 4. Two additional neuronal groups were identified: silent neurones having no spontaneous firing rates and EPSP-driven neurones having action potentials that are primarily dependent on excitatory synaptic input from nearby neurones. Silent neurones had the most extensive dendritic trees, and these branched in all directions. In contrast, EPSP-driven neurones had the fewest dendrites, and usually the dendrites were oriented in only one direction (either medially or laterally), suggesting that these neurones receive more selective synaptic input.

Gating and Braking of Short- and Long-Term Modulatory Effects by Interactions between Colocalized Neuromodulators

Spinal locomotor networks in the lamprey are modulated by tachykinin neuropeptides. A single 10 min application of the tachykinin substance P evokes a short-term ( approximately 1 hr) presynaptic facilitation of glutamate release and the postsynaptic potentiation of NMDA responses. The latter effect induces a long-term (>24 hr) protein synthesis-dependent increase in the frequency of network activity. Tachykinins are contained in a ventromedial spinal plexus into which the medial dendrites of network neurons project. Neurons in this plexus also contain colocalized dopamine and 5-HT. Here, dynamic plasticity evoked by modulator interactions has been examined by investigating the effects of 5-HT and dopamine on specific cellular, synaptic, and network effects of substance P. Preapplied 5-HT blocked the substance P-mediated increase in the network burst frequency and the potentiation of NMDA-evoked cellular responses that underlies its induction. 5-HT also blocked the presynaptic facilitation of glutamatergic synaptic transmission by substance P. The presynaptic, but not postsynaptic, effect of 5-HT was reduced by the protein phosphatase 2B inhibitor cypermethrin. Dopamine did not directly modulate the effects of substance P. However, it reduced the presynaptic interactive effect of 5-HT and thus gated the presynaptic potentiation of glutamatergic inputs by substance P. However, the substance P-mediated potentiation of NMDA responses was not gated by dopamine, and thus the long-term network modulation was not induced. Neuromodulator effects and their interactions can thus be modulated. By selecting components from the modulatory repertoire of substance P, these interactions evoke dynamic changes in short- and long-term synaptic and network plasticity.

Synaptogenesis in the giant-fibre system of Drosophila: interaction of the giant fibre and its major motorneuronal target.

The tergotrochanteral (jump) motorneuron is a major synaptic target of the Giant Fibre in Drosophila. These two neurons are major components of the fly's Giant-Fibre escape system. Our previous work has described the development of the Giant Fibre in early metamorphosis and the involvement of the shaking-B locus in the formation of its electrical synapses. In the present study, we have investigated the development of the tergotrochanteral motorneuron and its electrical synapses by transforming Drosophila with a Gal4 fusion construct containing sequences largely upstream of, but including, the shaking-B(lethal) promoter. This construct drives reporter gene expression in the tergotrochanteral motorneuron and some other neurons. Expression of green fluorescent protein in the motorneuron allows visualization of its cell body and its subsequent intracellular staining with Lucifer Yellow. These preparations provide high-resolution data on motorneuron morphogenesis during the first half of pupal development. Dye-coupling reveals onset of gap-junction formation between the tergotrochanteral motorneuron and other neurons of the Giant-Fibre System. The medial dendrite of the tergotrochanteral motorneuron becomes dye-coupled to the peripheral synapsing interneurons between 28 and 32 hours after puparium formation. Dye-coupling between tergotrochanteral motorneuron and Giant Fibre is first seen at 42 hours after puparium formation. All dye coupling is abolished in a shaking-B(neural) mutant. To investigate any interactions between the Giant Fibre and the tergotroachanteral motorneuron, we arrested the growth of the motorneuron's medial neurite by targeted expression of a constitutively active form of Dcdc42. This results in the Giant Fibre remaining stranded at the midline, unable to make its characteristic bend. We conclude that Giant Fibre morphogenesis normally relies on fasciculation with its major motorneuronal target.

Effects of unilateral cochlear removal on dendrites in the gerbil medial superior olivary nucleus.

For most neurons, dendrites serve as the major pathway for incoming activity from other neurons. It might therefore be expected that dendrites are particularly sensitive to variations in the level of afferent input they receive. In the auditory brainstem, this expectation has been confirmed in neurons of the medial superior olivary nucleus (MSO). The MSO is uniquely suited to studies of afferent influences on dendrites, as lateral and medial dendrites of MSO neurons receive inputs almost exclusively from the ipsilateral and contralateral ears, respectively. Thus, the effects of unilateral afferent manipulations may be compared between defined dendrites on the same neurons. We have used unilateral deafening (by surgical destruction of the cochlea) in immature [postnatal day 18 (P18)] and adult gerbils to study the late maturation and effect of peripheral deafferentation on the dendrites of MSO neurons. In semi-thin, frontal sections from unoperated animals, we found a change between P18 and adulthood from a lateral to a medial bias in the symmetry of MSO dendrites. Cochlear removal in adulthood led to a reduction in the density of dendritic profiles on the side of the ablation in both MSOs. Cochlear removal at P18 led to a rapid (< 3 days) and sustained dendritic atrophy that was most marked in the caudal part of the nucleus. Electron microscope (EM) measurements in the sagittal plane on MSO dendrite profiles of animals unilaterally deafened at P18 showed a reduction in the number, but not in the area, of profiles on the side of the deafened ear. These results demonstrate a developmental change in the symmetry of MSO medial and lateral dendrites, and a rapid and long-lasting reduction in the number of distal dendrites produced by unilateral deafening either in infancy or adulthood.

Local facilitation of plateau potentials in dendrites of turtle motoneurones by synaptic activation of metabotropic receptors

1. The spatial distribution of synaptic facilitation of plateau potentials in dendrites of motoneurones was investigated in transverse sections of the spinal cord of the turtle using differential polarization by applied electric fields. 2. The excitability of motoneurones in response to depolarizing current pulses was increased following brief activation of either the dorsolateral funiculus (DLF) or the medial funiculus (MF) even when synaptic potentials were eliminated by antagonists of ionotropic receptors. 3. The medial and lateral compartments of motoneurones were differentially polarized by the electric field generated by passing current between two electrodes on either side of the preparation. In one direction of the field lateral dendrites were depolarized while the cell body and medial dendrites were hyperpolarized (S- configuration). With current in the opposite direction the cell body and medial dendrites were depolarized while lateral dendrites were hyperpolarized (S + configuration). 4. Following brief activation of the DLF the excitability and the generation of plateau potentials were facilitated during differential depolarization of the lateral dendrites but not during differential depolarization of the cell body and medial dendrites. Following brief activation of the MF the excitability and generation of plateau potentials were facilitated during differential depolarization of the cell body and medial dendrites but not during differential depolarization of the lateral dendrites. 5. It is concluded that the synaptic facilitation of the dihydropyridine-sensitive response to depolarization is compartmentalized in turtle motoneurones.