Target cell contact suppresses neurite outgrowth from soma-soma paired Lymnaea neurons

Neurite extension from developing and/or regenerating neurons is terminated on contact with their specific synaptic partner cells. However, a direct relationship between the effects of target cell contact on neurite outgrowth suppression and synapse formation has not yet been demonstrated. To determine whether physical/synaptic contacts affect neurite extension from cultured cells, we utilized soma-soma synapses between the identified Lymnaea neurons. A presynaptic cell (right pedal dorsal 1, RPeD1) was paired either with its postsynaptic partner cells (visceral dorsal 4, VD4, and Visceral dorsal 2, VD2) or with a non-target cell (visceral dorsal 1, VD1), and the interactions between their neurite outgrowth patterns and synapse formation were examined. Specifically, when cultured in brain conditioned medium (CM, contains growth-promoting factors), RPeD1, VD4, and VD2 exhibited robust neurite outgrowth within 12-24 h of their isolation. Synapses, similar to those seen in vivo, developed between the neurites of these cells. RPeD1 did not, however, synapse with its non-target cell VD1, despite extensive neuritic overlap between the cells. When placed in a soma-soma configuration (somata juxtaposed against each other), appropriate synapses developed between the somata of RPeD1 and VD4 (inhibitory) and between RPeD1 and VD2 (excitatory). Interestingly, pairing RPeD1 with either of its synaptic partner (VD4 or VD2) resulted in a complete suppression of neurite outgrowth from both pre- and postsynaptic neurons, even though the cells were cultured in CM. A single cell in the same dish, however, extended elaborate neurites. Similarly, a postsynaptic cell (VD4) contact suppressed the rate of neurite extension from a previously sprouted RPeD1. This suppression of the presynaptic growth cone motility was also target cell contact specific. The neurite suppression from soma-soma paired cells was transient, and neuronal sprouting began after a delay of 48-72 h. In contrast, when paired with VD1, both RPeD1 and this non-target cell exhibited robust neurite outgrowth. We demonstrate that this neurite suppression from soma-soma paired cells was target cell contact/synapse specific and Ca(2+) dependent. Specifically, soma-soma pairing in CM containing either lower external Ca(2+) concentration (50% of its control level) or Cd(2+) resulted in robust neurite outgrowth from both cells; however, the incidence of synapse formation between the paired cells was significantly reduced. Taken together, our data show that contact (physical and/or synaptic) between synaptic partners strongly influence neurite outgrowth patterns of both pre- and postsynaptic neurons in a time-dependent and cell-specific manner. Moreover, our data also suggest that neurite outgrowth and synapse formation are differentially regulated by external Ca(2+) concentration.     

Target cell contact suppresses neurite outgrowth from soma–soma paired Lymnaea neurons

Neurite extension from developing and/or regenerating neurons is terminated on contact with their specific synaptic partner cells. However, a direct relationship between the effects of target cell contact on neurite outgrowth suppression and synapse formation has not yet been demonstrated. To determine whether physical/synaptic contacts affect neurite extension from cultured cells, we utilized soma–soma synapses between the identified Lymnaea neurons. A presynaptic cell (right pedal dorsal 1, RPeD1) was paired either with its postsynaptic partner cells (visceral dorsal 4, VD4, and Visceral dorsal 2, VD2) or with a non‐target cell (visceral dorsal 1, VD1), and the interactions between their neurite outgrowth patterns and synapse formation were examined. Specifically, when cultured in brain conditioned medium (CM, contains growth‐promoting factors), RPeD1, VD4, and VD2 exhibited robust neurite outgrowth within 12–24 h of their isolation. Synapses, similar to those seen in vivo, developed between the neurites of these cells. RPeD1 did not, however, synapse with its non–target cell VD1, despite extensive neuritic overlap between the cells. When placed in a soma–soma configuration (somata juxtaposed against each other), appropriate synapses developed between the somata of RPeD1 and VD4 (inhibitory) and between RPeD1 and VD2 (excitatory). Interestingly, pairing RPeD1 with either of its synaptic partner (VD4 or VD2) resulted in a complete suppression of neurite outgrowth from both pre‐ and postsynaptic neurons, even though the cells were cultured in CM. A single cell in the same dish, however, extended elaborate neurites. Similarly, a postsynaptic cell (VD4) contact suppressed the rate of neurite extension from a previously sprouted RPeD1. This suppression of the presynaptic growth cone motility was also target cell contact specific. The neurite suppression from soma–soma paired cells was transient, and neuronal sprouting began after a delay of 48–72 h. In contrast, when paired with VD1, both RPeD1 and this non‐target cell exhibited robust neurite outgrowth. We demonstrate that this neurite suppression from soma–soma paired cells was target cell contact/synapse specific and Ca²⁺ dependent. Specifically, soma–soma pairing in CM containing either lower external Ca²⁺ concentration (50% of its control level) or Cd²⁺ resulted in robust neurite outgrowth from both cells; however, the incidence of synapse formation between the paired cells was significantly reduced. Taken together, our data show that contact (physical and/or synaptic) between synaptic partners strongly influence neurite outgrowth patterns of both pre‐ and postsynaptic neurons in a time‐dependent and cell‐specific manner. Moreover, our data also suggest that neurite outgrowth and synapse formation are differentially regulated by external Ca²⁺ concentration. © 2000 John Wiley & Sons, Inc. J Neurobiol 42: 357–369, 2000     

Localization,physiology, and modulation of a molluskan dopaminergic synapse

We investigated the location, physiology, and modulation of an identified synapse from the central nervous system (CNS) of the mollusk Lymnaea stagnalis. Specifically, the excitatory synapse from interneuron right pedal dorsal one (RPeD1) to neurons visceral dorsal two and three (VD2/3) was examined. The gross and fine morphology of these neurons was determined by staining with Lucifer yellow or sulforhodamine. In preparations where RPeD1 was stained with Lucifer yellow and VD2/3 with sulfo-rhodamine, the axon collaterals occupied similar regions, suggesting that these neurons make physical contact in the CNS. Digital confocal microscopy of these preparations revealed that presynaptic varicosities made apparent contact (synapses) with smooth postsynaptic axon collaterals. The number of putative synapses per preparation was about five to 10. Regarding physiology, the synaptic latency was moderately rapid at 24.1 ± 5.2 ms. Previous work indicated that RPeD1 uses dopamine as a neurotransmitter. The RPeD1 → VD2/3 excitatory postsynaptic potential (EPSP) and the VD2/3 bath-applied dopamine (100-μM) response displayed a similar decrease in input resistance and a similar predicted reversal potential (−31 vs. −26 mV), indicating that the synapse and exogenous dopamine activate the same conductance. Finally, bath-applied serotonin (10 μM) rapidly and reversibly depressed the RPeD1 → VD2/3 synapse but did not affect the VD2/3 bath-applied dopamine (100-μM) response, suggesting a presynaptic locus of action for serotonin. The effect of serotonin was not associated with any changes to the pre- or postsynaptic membrane potential and input resistance, or the presynaptic action potential half-width. The RPeD1 → b3 VD2/3 synapse provides an opportunity to examine the anatomy and physiology of transmission, and is amenable to the study of neuromodulation. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 247–264, 1997     

Pronase modifies synaptic transmission and activity of identifiedLymnaea neurons

Proteolytic enzymes can have significant effects on the physiological properties of neurons. Although several actions of proteolytic enzymes on the physiology of single neurons have been described, the effects of these enzymes on network properties in the central nervous system (CNS) have received less attention. The effects of bath-applied pronase (0.05%) on synaptic connections and spontaneous activity in theLymnaea CNS were examined. Brief application (i.e. 2–3 min) of pronase modified some, but not all, synapses in the CNS. For example, the chemical synapse between two interneurons, RPeD11 and RPeD1, and between the interneuron, RPeD1, and RPA motoneurons were examined. Both these synapses were either biphasic or monophasic (depolarizing) under control conditions. Pronase exposure eliminated the depolarizing phase of the RPeD11→RPeD1 synapse, but had no effect on the connection between RPeD1 and RPA neurons. In addition, the effects of pronase on electrical-coupling between two peptidergic neurons, VD1 and RPD2, in the CNS were investigated. Pronase decreased the total network input resistance and cell input resistances as well as the steady-state coupling ratio. Furthermore, exposure to pronase induced various changes (i.e. depolarization, hyperpolarization, bursting patterns and afterdischarges) in the activity pattern of different identified neurons in the CNS. Collectively, these data show that even brief exposure to a low concentration of pronase can acutely modify both synapses and neuronal activity.     

Different extrinsic trophic factors regulate neurite outgrowth and synapse formation between identified Lymnaea neurons

The requirement for trophic factors in neurite outgrowth is well established, though their role in synapse formation is yet to be determined. Moreover, the issue of whether the trophic factors mediating neurite outgrowth are also responsible for synapse specification has not yet been resolved. To test whether trophic factors mediating neurite outgrowth and synapse formation between identified neurons are conserved in two molluscan species and whether these developmental processes are differentially regulated by different trophic factors, we used soma-soma and neurite-neurite synapses between identified Lymnaea neurons. We demonstrate here that the trophic factors present in Aplysia hemolymph, although sufficient to induce neurite outgrowth from Lymnaea neurons, do not promote specific synapse formation between excitatory partners. Specifically, the identified presynaptic neuron visceral dorsal 4 (VD4) and postsynaptic neuron left pedal dorsal 1 (LPeD1) were either paired in a soma-soma configuration or plated individually to allow neuritic contacts. Cells were cultured in either Lymnaea brain-conditioned medium (CM) or on poly-L-lysine dishes that were pretreated with Aplysia hemolymph (ApHM), but contained only Lymnaea defined medium (DM; does not promote neurite outgrowth). In ApHM-coated dishes containing DM, Lymnaea neurons exhibited extensive neurite outgrowth, but appropriate excitatory synapses failed to develop between the cells. Instead, inappropriate reciprocal inhibitory synapses formed between VD4 and LPeD1. Similar inappropriate inhibitory synapses were observed in Aplysia hemolymph-pretreated dishes that contained dialyzed Aplysia hemolymph. These inhibitory synapses were novel and inappropriate, because they do not exist in vivo. A receptor tyrosine kinase inhibitor (Lavendustin A) blocked neurite outgrowth induced by both Lymnaea CM and ApHM. However, it did not affect inappropriate inhibitory synapse formation between the neurons. These data demonstrate that neurite outgrowth but not inappropriate inhibitory synapse formation involves receptor tyrosine kinases. Together, our data provide direct evidence that trophic factors required for neurite outgrowth are conserved among two different molluscan species, and that neurite extension and synapse specification between excitatory partners are likely mediated by different trophic factors.     

Dopamine-mediated calcium channel regulation in synaptic suppression in L. stagnalis interneurons

D2 dopamine receptor-mediated suppression of synaptic transmission from interneurons plays a key role in neurobiological functions across species, ranging from respiration to memory formation. In this study, we investigated the mechanisms of D2 receptor-dependent suppression using soma-soma synapse between respiratory interneuron VD4 and LPeD1 in the mollusk Lymnaea stagnalis (L. stagnalis). We studied the effects of dopamine on voltage-dependent Ca²⁺ current and synaptic vesicle release from the VD4. We report that dopamine inhibits voltage-dependent Ca²⁺ current in the VD4 by both voltage-dependent and -independent mechanisms. Dopamine also suppresses synaptic vesicle release downstream of activity-dependent Ca²⁺ influx. Our study demonstrated that dopamine acts through D2 receptors to inhibit interneuron synaptic transmission through both voltage-dependent Ca²⁺ channel-dependent and -independent pathways. Taken together, these findings expand our understanding of dopamine function and fundamental mechanisms that shape the dynamics of neural circuit.     

Repetitive noxious stimulus altered the shadow-induced withdrawal behavior in Lymnaea

Stress alters adaptive behaviors including vigilance behaviors. In Lymnaea one of these vigilance behavior is a heightened withdrawal response to a shadow. The shadow withdrawal response (SWR) is mediated by dermal photoreceptors located primarily on the foot, mantle cavity, and skin around the pneumostome area. Here we asked whether we could obtain a neural correlate of the heightened SWR and other essential behaviors following traumatic stress. We measured the electrophysiological properties of 'Right Pedal Dorsal 11 (RPeD11)', the interneuron that plays a major role in mediating the whole-body withdrawal response. In traumatized snails 24 hours after the trauma they responded not only to a shadow stimulus with an augmented withdrawal response, but suppressed in locomotive, feeding and respiratory behavior. Their behavioral change lasted at least one week. Accompanying the behavioral change in these 'traumatized' preparations there are a number of significant changes in the neuronal properties of RPeD11 compared to na?ve preparations. For example, RPeD11 is significantly more depolarized (～10 mV) has significantly larger input resistance, and the duration of the response elicited by the shadow persists longer. All these changes result in an increased RPeD11 response and seem to raise their defensive alert level.     

Excitatory actions of propofol and ketamine in the snail Lymnaea stagnalis

This study compares the actions of the intravenous anaesthetics propofol and ketamine on animal behaviour and neuronal activity in the snail Lymnaea stagnalis, particularly in relation to excitatory effects observed clinically. When injected into the whole animal, neither agent induced total anaesthesia. Rather, behavioural activity was enhanced by propofol (10(-5) M) and ketamine (10(-7) M), indicating excitatory effects. When superfused over the isolated central nervous system (CNS), differential effects were produced in two identified neurons, right pedal dorsal 1 (RPeD1) and visceral dorsal 4 (VD4). Resting membrane properties were largely unaffected. However, spike after hyperpolarisation was significantly reduced in RPeD1, but not VD4, with some evidence of increased excitability. In addition, an intrinsic bursting property (post-stimulus burst) in VD4 was altered by propofol (10(-7) M). The results suggest significant excitatory components in the actions of some intravenous anaesthetics, as well as a potential role in modifying excitation and bursting mechanisms in the CNS.     

Probabilistic secretion of quanta in the central nervous system: granule cell synaptic control of pattern separation and activity regulation.

The implications of probabilistic secretion of quanta for the functioning of neural networks in the central nervous system have been explored. A model of stochastic secretion at synapses in simple networks, consisting of large numbers of granule cells and a relatively small number of inhibitory interneurons, has been analysed. Such networks occur in the input to the cerebellum Purkinje cells as well as to hippocampal CA3 pyramidal cells and to pyramidal cells in the visual cortex. In this model the input axons terminate on granule cells as well as on an inhibitory interneuron that projects to the granule cells. Stochastic secretion at these synapses involves both temporal variability in secretion at single synapses in the network as well as spatial variability in the secretion at different synapses. The role of this stochastic variability in controlling the size of the granule cell output to a level independent of the size of the input and in separating overlapping inputs has been determined analytically as well as by simulation. The regulation of granule-cell output activity to a reasonably constant value for different size inputs does not occur in the absence of an inhibitory interneuron when both spatial and temporal stochastic variability occurs at the remaining synapses; it is still very poor in the presence of such an interneuron but in the absence of stochastic variability. However, quite good regulation is achieved when the inhibitory interneuron is present with spatial and temporal stochastic variability of secretion at synapses in the network. Excellent regulation is achieved if, in addition, allowance is made for the nonlinear behaviour of the input-output characteristics of inhibitory interneurons. The capacity of granule-cell networks to separate overlapping patterns of activity on their inputs is adequate, with spatial variability in the secretion at synapses, but is improved if there is also temporal variability in the stochastic secretion at individual synapses, although this is at the expense of reliability in the network. Other factors which improve pattern separation are control of the output to very low activity levels, and a restriction on the cumulative size of the excitatory input terminals of each granule cell. Application of the theory to the input neural networks of the cerebellum and the hippocampus shows the role of stochastic variability in quantal transmission in determining the capacity of these networks for pattern separation and activity regulation.     

Helping thy neighbors: spillover at the mossy fiber glomerulus

Neurotransmitter "spillover" between neighboring synapses challenges the principle of synapse specificity. In this issue of Neuron, show that release from neighboring presynaptic sites contributes significantly to AMPA receptor-mediated postsynaptic currents at cerebellar mossy fiber synapses. Unexpectedly, spillover is predicted to improve the reliability and reduce the variability of transmission at this glomerular synapse.     

Acid-Base Balance Modulates Respiratory and Alimentary Behavior of the Mollusc Lymnaea stagnalis

An active reaction (change of pH) in hemolymph of the freshwater pulmonate mollusc Lymnaea stagnalis is studied in various physiological states: hunger, satiety, and alimentary excitation. In satiated animals the hemolymph pH is shifted to the acid area (7.6 ± 0.003) as compared with hungry animals (7.9 ± 0.05). The satiated individuals are characterized by an increased respiratory activity and decreased food consumption as compared with hungry animals. Acidification of the medium leads to an increase of excitability of the respiratory network interneurons (RPeD1, VD4, VD1/RPD2) and to inhibition of activity of the alimentary network interneurons (R/L CGC), whereas alkalization, to opposite effects. It is suggested that pH is one of factors coordinating activity of functional systems of Lymnaea stagnalis due to effect on neuronal correlates of the respiratory and alimentary behavior.     

The influences of somatic and dendritic inhibition on bursting patterns in a neuronal circuit model

The balance between inhibition and excitation plays a crucial role in the generation of synchronous bursting activity in neuronal circuits. In human and animal models of epilepsy, changes in both excitatory and inhibitory synaptic inputs are known to occur. Locations and distribution of these excitatory and inhibitory synaptic inputs on pyramidal cells play a role in the integrative properties of neuronal activity, e.g., epileptiform activity. Thus the location and distribution of the inputs onto pyramidal cells are important parameters that influence neuronal activity in epilepsy. However, the location and distribution of inhibitory synapses converging onto pyramidal cells have not been fully studied. The objectives of this study are to investigate the roles of the relative location of inhibitory synapses on the dendritic tree and soma in the generation of bursting activity. We investigate influences of somatic and dendritic inhibition on bursting activity patterns in several paradigms of potential connections using a simplified multicompartmental model. We also investigate the effects of distribution of fast and slow components of GABAergic inhibition in pyramidal cells. Interspike interval (ISI) analysis is used for examination of bursting patterns. Simulations show that the inhibitory interneuron regulates neuronal bursting activity. Bursting behavior patterns depend on the synaptic weight and delay of the inhibitory connection as well as the location of the synapse. When the inhibitory interneuron synapses on the pyramidal neuron, inhibitory action is stronger if the inhibitory synapse is close to the soma. Alterations of synaptic weight of the interneuron can be compensatory for changes in the location of synaptic input. The relative changes in these parameters exert a considerable influence on whether synchronous bursting activity is facilitated or reduced. Additional simulations show that the slow GABAergic inhibitory component is more effective than the fast component in distal dendrites. Taken together, these findings illustrate the potential for GABAergic inhibition in the soma and dendritic tree to play an important modulatory role in bursting activity patterns.     

Intra-synapse-type and inter-synapse-type relationships between synaptic size and AMPAR expression

To gain insights into structure-function relationship of excitatory synapses, we revisit our quantitative analysis of synaptic AMPAR by highly sensitive freeze-fracture replica labeling in eight different connections. All of these connections showed linear correlation between synapse size and AMPAR number indicating a common intra-synapse-type relationship in CNS synapses. On the contrary, inter-synapse-type relationship is unexpected indicating no correlation between averages of synapse size and AMPAR number. Interestingly, connections with large average synapse size and low AMPAR density showed high variability of AMPAR number and mosaic distribution within the postsynaptic membrane. We propose an idea that these connections may quickly exhibit synaptic plasticity by modifying AMPAR density/number whereas those with high AMPAR density change their efficacy by modifying synapse size.     

Temperature dependence of monoamine-induced pulmonary respiration in the mollusc <Emphasis Type="Italic">Lymnaea stagnalis</Emphasis>

Pulmonary respiration (spontaneous and mediated by intracavitary administration of monoamines) has been studied in molluscs at different ambient temperatures (5, 15, and 25°C). Monoamines (dopamine, serotonin, and adrenaline) were established not to broaden the temperature diapason realization of the respiratory behavior. Microelectrode studies of the spontaneous electrical activity of the Lymnaea stagnalis respiratory network neurons (RPeD1, VD4, and Vi-cluster cells) revealed that both spontaneous and monoamine-induced respiration programs had been terminated under hypothermia conditions. The indicated effects are suggested to be due to the temperature dependence of the chemical, predominantly peptidergic, transmission of signal between neurons of the central respiratory rhythm generator in Lymnaea.     

Target neuron specification of short-term synaptic facilitation and depression in the cricket CNS

We investigated the role of retrograde signals in the regulation of short-term synaptic depression and facilitation by characterizing the form of plasticity expressed at novel synapses on four giant interneurons in the cricket cercal sensory system. We induced the formation of novel synapses by transplanting a mesothoracic leg and its associated sensory neurons to the cricket terminal abdominal segment. Axons of ectopic leg sensory neurons regenerated and innervated the host terminal abdominal ganglion forming monosynaptic connections with the medial giant interneuron (MGI), lateral giant interneuron (LGI), and interneurons 7-1a and 9-2a. The plasticity expressed by these synapses was characterized by stimulating a sensory neuron with pairs of stimuli at various frequencies or with trains of 10 stimuli delivered at 100 Hz and measuring the change in excitatory postsynaptic potential amplitude recorded in the postsynaptic neuron. Novel synapses of a leg tactile hair on 7-1a depressed, as did control synapses of cercal sensory neurons on this interneuron. Novel synapses of leg campaniform sensilla (CS) sensory neurons on MGI, like MGI's control synapses, always facilitated. The form of plasticity expressed by novel synapses is thus consistent with that observed at control synapses. Leg CS synapses with 9-2a also facilitated; however, the plasticity expressed by these sensory neurons is dependent on the identity of the postsynaptic cell since the synapses these same sensory neurons formed with LGI always depressed. We conclude that the form of plasticity expressed at these synaptic connections is determined retrogradely by the postsynaptic cell. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 700–714, 1998     

Cerebellin–neurexin complexes instructing synapse properties

Cerebellins (Cbln1-4) are secreted adaptor proteins that connect presynaptic neurexins (Nrxn1-3) to postsynaptic ligands (GluD1/2 for Cbln1-3 vs. DCC and Neogenin-1 for Cbln4). Classical studies demonstrated that neurexin-Cbln1-GluD2 complexes organize cerebellar parallel-fiber synapses, but the role of cerebellins outside of the cerebellum has only recently been clarified. In synapses of the hippocampal subiculum and prefrontal cortex, Nrxn1-Cbln2-GluD1 complexes strikingly upregulate postsynaptic NMDA-receptors, whereas Nrxn3-Cbln2-GluD1 complexes conversely downregulate postsynaptic AMPA-receptors. At perforant-path synapses in the dentate gyrus, in contrast, neurexin/Cbln4/Neogenin-1 complexes are essential for LTP without affecting basal synaptic transmission or NMDA- or AMPA-receptors. None of these signaling pathways are required for synapse formation. Thus, outside of the cerebellum neurexin/cerebellin complexes regulate synapse properties by activating specific downstream receptors.     

Temperature dependence of monoamine-induced pulmonary respiration of mollusc Lymnaea stagnalis

Pulmonary respiration of molluscs (spontaneous and mediated by intracavital injection of monoamines) was studied at different environmental temperatures (5, 15, and 25 degrees C). It was established that monoamines (dopamine, serotonin, adrenalin) did not enlarge the temperature diapason, in which the respiratory behavior was realized. Microelectrode studies of spontaneous electrical activity of neurons from the respiratory network of Lymnaea stagnalis (RPeD1, VD4, cells of the Vi cluster) have shown that the respiratory program, both spontaneous and the monoamine-induced, is terminated in hypothermia. The indicated effects are suggested to be due to temperature dependence of the chemical, predominantly peptidergical, transmission of signal between neurons of the central pattern generator of respiratory pattern in Lymnaea.     

Dapper Antagonist of Catenin-1 Cooperates with Dishevelled-1 during Postsynaptic Development in Mouse Forebrain GABAergic Interneurons

Synaptogenesis has been extensively studied along with dendritic spine development in glutamatergic pyramidal neurons, however synapse development in cortical interneurons, which are largely aspiny, is comparatively less well understood. Dact1, one of 3 paralogous Dact (Dapper/Frodo) family members in mammals, is a scaffold protein implicated in both the Wnt/β-catenin and the Wnt/Planar Cell Polarity pathways. We show here that Dact1 is expressed in immature cortical interneurons. Although Dact1 is first expressed in interneuron precursors during proliferative and migratory stages, constitutive Dact1 mutant mice have no major defects in numbers or migration of these neurons. However, cultured cortical interneurons derived from these mice have reduced numbers of excitatory synapses on their dendrites. We selectively eliminated Dact1 from mouse cortical interneurons using a conditional knock-out strategy with a Dlx-I12b enhancer-Cre allele, and thereby demonstrate a cell-autonomous role for Dact1 during postsynaptic development. Confirming this cell-autonomous role, we show that synapse numbers in Dact1 deficient cortical interneurons are rescued by virally-mediated re-expression of Dact1 specifically targeted to these cells. Synapse numbers in these neurons are also rescued by similarly targeted expression of the Dact1 binding partner Dishevelled-1, and partially rescued by expression of Disrupted in Schizophrenia-1, a synaptic protein genetically implicated in susceptibility to several major mental illnesses. In sum, our results support a novel cell-autonomous postsynaptic role for Dact1, in cooperation with Dishevelled-1 and possibly Disrupted in Schizophrenia-1, in the formation of synapses on cortical interneuron dendrites.     

Differential modulation of chemical and electrical components of mixed synapses in the lobster stomatogastric ganglion

1. Two pairs of neurons in the pyloric network of the spiny lobster, Panulirus interruptus, communicate through mixed graded chemical and rectifying electrical synapses. The anterior burster (AB) chemically inhibits and is electrically coupled to the ventricular dilator (VD); the lateral pyloric (LP) and pyloric (PY) neurons show reciprocal chemical inhibition and electrical coupling. We examined the effects of dopamine (DA), serotonin (5HT) and octopamine (Oct) on these mixed synapses to determine the plasticity possible with opposing modes of synaptic interaction.
2. Dopamine increased net inhibition at all three pyloric mixed synapses by both reducing electrical coupling and increasing chemical inhibition. This reversed the sign of the net synaptic interaction when electrotonic coupling dominated some mixed synapses, and activated silent chemical components of other mixed synapses.
3. Serofonin weakly enhanced LP → PY net inhibition, by reducing electrical coupling without altering chemical inhibition. Serotonin reduced AB→ VD electrical coupling, but variability in its effect on the chemical component made the net effect non-significant.
4. Octopamine enhanced LP→ PY and PY→ LP net inhibition by enhancing the chemical inhibitory component without altering electrical coupling.
5. Differential modulation of chemical and electrical components of mixed synapses markedly changes the net synaptic interactions. This contributes to the flexible outputs that modulators evoke from anatomically defined neural networks.