Biomedical subjects

S Schacher

Publications and source records attributed to S Schacher.

At least 19 recordsLinked to original sources

PubMed1999

En passant synaptic varicosities form directly from growth cones by transient cessation of growth cone advance but not of actin-based motility.

Formation of terminal synapses at sites such as the neuromuscular junction involves transformation of the motile growth cone into the nonmotile synaptic terminal. However, transformation does not need to be the mechanism when a neurite forms multiple widely spaced synaptic varicosities along a target in an en passant configuration. Synaptic varicosities could form here by specialization of the neurite after the growth cone has advanced past the site. We examined this issue by using cocultures of identified sensory (SN) and motor (L7) neurons from Aplysia. Living SNs were labeled with fluorescent dye and their neurites were observed at high resolution every few minutes growing along the axon of L7, allowing a fine-grained analysis of the behavior of the growth cone at the sites of synapse formation. All varicosities whose formation was observed indeed developed from the growth cone. Sensory varicosities were shown by electron microscopy to contain features characteristic of active zones for transmitter release within a day of their formation on the motor axon. Growth cone advance slowed or stopped transiently during varicosity formation, but the motile activity of the peripheral region of the growth cone (veils and filopodia) was maintained. These results suggest that target "stop signals" involved in the formation of synapses, at least of the en passant variety, may be of a different type from the growth inhibitory molecules, such as the collapsins, which guide axons to their targets.

Actins↗

PubMed1999

Expression and branch-specific export of mRNA are regulated by synapse formation and interaction with specific postsynaptic targets.

Mechanosensory neurons (SNs) of Aplysia form synapses in culture with some targets (L7), but not others (L11), even when a SN is plated with both targets. We examined whether branch-specific net export of mRNA encoding synapse-specific molecules might contribute to branch-specific synapse formation. Single-cell RT-PCR was used to assay levels of mRNA encoding the SN-specific neuropeptide (sensorin A) and other transcripts in cell bodies and neuritic processes of SNs cultured alone or with synaptic targets. Some mRNAs are exported to neurites, but not others. Sensorin A mRNA is detected only in SN cell bodies and neurites, and expression levels correlate with the strength of the synaptic connections formed with L7 after 4 d in culture. After 4 d, more sensorin A transcripts are detected in SN neurites contacting L7 than in SN neurites contacting L11. The differential expression at 4 d is found even when a single SN contacts both targets simultaneously. By contrast, no significant difference in expression is detected in SN neurites contacting L7 versus L11 after 1 d of coculture. The results suggest that interaction and synapse formation with a specific target lead to a time-dependent change in the branch-specific accumulation of sensorin A mRNA in SNs. Because local protein synthesis at synaptic sites might contribute to synaptic function or plasticity, the results suggest that branch-specific targeting of mRNA encoding synapse-related molecules may contribute to the formation of specific synapses.

Animals↗

PubMed1999

Mechanisms for generating the autonomous cAMP-dependent protein kinase required for long-term facilitation in Aplysia.

The formation of a persistently active cAMP-dependent protein kinase (PKA) is critical for establishing long-term synaptic facilitation (LTF) in Aplysia. The injection of bovine catalytic (C) subunits into sensory neurons is sufficient to produce protein synthesis-dependent LTF. Early in the LTF induced by serotonin (5-HT), an autonomous PKA is generated through the ubiquitin-proteasome-mediated proteolysis of regulatory (R) subunits. The degradation of R occurs during an early time window and appears to be a key function of proteasomes in LTF. Lactacystin, a specific proteasome inhibitor, blocks the facilitation induced by 5-HT, and this block is rescued by injecting C subunits. R is degraded through an allosteric mechanism requiring an elevation of cAMP coincident with the induction of a ubiquitin carboxy-terminal hydrolase.

Animals↗

PubMed1999

Changes in functional glutamate receptors on a postsynaptic neuron accompany formation and maturation of an identified synapse.

N-Methyl-D-aspartate (NMDA)-type glutamate receptors play important roles at developing synapses and in activity-dependent synaptic plasticity. Recent studies in Aplysia suggest that NMDA-like receptors may contribute to some forms of plasticity of sensorimotor synapses accompanying associative learning. We examined at various times after plating neurons in culture the contribution of NMDA- and alpha-amino-3 hydroxy-5 methyl-4 isoxazole proprionic acid (AMPA)-like glutamate receptors to responses evoked in motor cell L7 either by action potentials in sensory neurons (SNs) or by focal applications of glutamate. We found that (D,L)-2-amino-5-phosphopentoic acid-sensitive receptors contributed significantly to postsynaptic responses in 1-day cultures but contributed little in the same cultures on day 4. By contrast, postsynaptic responses on day 4 increased significantly in amplitude by the addition of functional 6-cyano-7 nitroquinoxaline-2,3-dione- or 1-(4-aminophenyl)-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepine hydrochloride-sensitive receptors. Receptors with NMDA-like properties are detected on day 1 only at sites on L7 apposed to SN varicosities, and are not detected on L7 cultured alone. The results indicate that changes in expression and distribution of functional receptors on L7 accompany the formation and maturation of SN synapses. Signals from the SN appear to trigger expression and clustering of functional NMDA-like receptors at sites contacted by presynaptic structures capable of transmitter release. With time, functional AMPA-like receptors are added to these sites enhancing synaptic efficacy. The results are consistent with the idea that the expression and sequential clustering of NMDA- and AMPA-type receptors may be essential for the formation and maturation of central synapses.

2-Amino-5-phosphonovalerate↗

PubMed1998

Binding of serotonin to receptors at multiple sites is required for structural plasticity accompanying long-term facilitation of Aplysia sensorimotor synapses.

Long-term changes in the efficacy of Aplysia sensorimotor synapses accompany nonassociative and associative forms of behavioral plasticity. This synapse expresses long-term facilitation either with repeated applications of 5-hydroxytryptamine (5-HT) or with a single pairing of tetanus in the sensory neuron (SN) and bath application of 5-HT. We examined whether structural changes in the SN accompany all forms of long-term synaptic enhancement and the locations at which 5-HT must bind receptors to evoke long-term functional and/or structural changes. Pairing tetanus with one application of 5-HT evoked both functional and structural changes after 24 hr only when 5-HT application was temporally paired with the tetanus and activated receptors on both the SN cell body and terminal region. Repeated application of 5-HT to the terminal region alone failed to evoke any long-term change. Repeated applications of 5-HT to the SN cell body alone evoked a change in synaptic efficacy at 24 hr but failed to increase SN varicosities. Repeated applications of 5-HT to both the SN cell body and the terminal region evoked increases in both synaptic efficacy and the number of SN varicosities at 24 hr. The results indicate that different external stimuli can evoke equivalent forms of long-term synaptic facilitation with or without structural changes in the SNs. Changes in the number of SN varicosities can accompany different forms of long-term facilitation and require the activation of 5-HT receptors at multiple sites.

Animals↗

PubMed1998

[Diagnosis of herpetic uveitis and keratouveitis].

BACKGROUND: In epithelial viral keratitis as in viral retinitis, the diagnosis is made on the basis of typical clinical findings. A laboratory confirmation is achieved in over 80% using routine laboratory methods. In contrast, it is almost impossible to confirm the diagnosis of stromal herpetic keratitis in vivo using the currently available laboratory methods. Nothing is known about the situation in cases of viral anterior uveitis. METHODS: Of 52 patients with granulomatous anterior uveitis, 31 were diagnosed on the basis of clinical findings as active herpetic uveitis (group 1), 14 as active granulomatous uveitis of unknown origin (group 2), and 7 had inactive disease after quietening down of herpetic uveitis (group 3). From all patients, aqueous humor was collected at the time of diagnosis and processed for viral culture, Herpes antigen ELISA, and amplification of viral DNA of HSV-1 and VZV. RESULTS: Viral growth in culture was found in only one case in group 3. In this group, viral antigen or viral DNA were detected in no case. Herpes antigen was found in 5/31 cases (16%) in group 1 and in 1/11 cases (9%) in group 2, and viral DNA was found in 8/31 cases from group 1 (5x HSV-1 and 3x VZV) and in 5/14 cases (31%) from group 2. After combination of antigen detection and DNA amplification, the presence of virus was confirmed in 14/45 cases (29%). CONCLUSION: Virus culture has not proven useful in the diagnosis of viral anterior segment disease. Despite their high overall sensitivity, neither antigen ELISA nor the amplification of viral DNA proved sensitive enough to establish a viral etiology. Nevertheless, a laboratory confirmation should be attempted in granulomatous uveitis of unknown origin after preclusion of an underlying systemic disease because of the consequences of a diagnosis of viral anterior segment disease for treatment and prognosis.

Antibodies, Viral↗

PubMed1997

Site-specific and sensory neuron-dependent increases in postsynaptic glutamate sensitivity accompany serotonin-induced long-term facilitation at Aplysia sensorimotor synapses.

Long-term changes in the efficacy of Aplysia sensory neuron (SN) connections accompany behavioral training or applications with 5-HT. The changes evoked by training or 5-HT include formation of new SN varicosities and transmitter release sites. Because new synapse formation requires proper alignment of presynaptic structures with postsynaptic zones containing a high density of transmitter receptors, we examined whether changes in postsynaptic sensitivity to the presumed SN transmitter (glutamate) were correlated with formation and distribution of new SN varicosities in contact with motor cell L7 in cell culture. The formation of stable SN connections after 4 d in culture did not significantly change overall responses to focal applications of glutamate. However, specific sites along L7's axon apposed to SN varicosities expressed larger responses to glutamate compared with adjacent sites with few SN varicosities. After treatments with 5-HT that evoked long-term changes in both the structure and the function of SN-L7 synaptic interaction, glutamate responses increased selectively at sites along the surface of L7's axon with preexisting or new SN varicosities. Increases in postsynaptic response to glutamate 24 hr after 5-HT treatment required interaction with an SN. These results suggest that new synapse formation between neurons, either with regeneration or after external stimuli that evoke increases in synaptic efficacy, involves site-specific changes in expression of functional neurotransmitter receptors on the postsynaptic cell that is regulated by interaction with the presynaptic neuron.

Animals↗

PubMed1997

Pathway-specific synaptic plasticity: activity-dependent enhancement and suppression of long-term heterosynaptic facilitation at converging inputs on a single target.

To explore mechanisms of long-term, pathway-specific synaptic plasticity, we examined consequences of differential stimulation of Aplysia sensorimotor connections in culture where two sensory neuron (SN) inputs converge on a single target motor cell L7. A single pairing of tetanus in one SN with bath application of 5-HT evoked long-term (24 hr) increase in efficacy of the SN connection given paired stimulation that was comparable in magnitude to the increase in synaptic efficacy evoked with repeated applications of 5-HT. Repeated pairing of tetanus in one SN with applications of 5-HT evoked a significant increase in efficacy of the SN connection given paired stimuli, and significant reduction in facilitation that is normally evoked by repeated applications of 5-HT in the unpaired SN connection. Hyperpolarization of L7 or incubation with APV interfered with both enhancement of facilitation with paired stimulation and suppression of facilitation with unpaired stimulation, but without interfering with long-term facilitation evoked either by repeated applications of 5-HT or by a single pairing. The results suggest that a single connection can undergo at least two forms of activity-dependent, pathway-specific facilitation lasting more than 24 hr. One form, evoked with a single pairing, is initiated and maintained primarily by activity in the presynaptic neuron. The other form, evoked with repeated paired stimuli, requires target-dependent activity that differentially modulates long-term heterosynaptic facilitation at the converging inputs.

2-Amino-5-phosphonovalerate↗

PubMed1996

Differential distribution of functional receptors for neuromodulators evoking short-term heterosynaptic plasticity in Aplysia sensory neurons.

Synaptic transmission and excitability in Aplysia sensory neurons (SNs) are bidirectionally modulated by 5-HT and FMRFamide. To explore the regional distribution of different functional receptors that modulate SN properties, we examined changes in synaptic efficacy and excitability with brief focal applications of the neuromodulators to different regions of SNs that have established connections with motor cell L7 in culture. Short-term changes in synaptic efficacy were evoked only when 5-HT or FMRFamide was applied to regions with SN varicosities along the surface of L7 axons. Applications to adjacent SN neurites with few varicosities in contact with L7 axons failed to evoke a significant change in synaptic efficacy. The distribution of functional receptors mediating changes in excitability differed for 5-HT and FMRFamide. Whereas excitability increases were evoked only when 5-HT was applied to SN cell bodies, excitability decreases in SNs were evoked only when FMRFamide was applied to regions along the L7 axon with SN varicosities. Without the target cell, cell bodies of SNs expressed both 5-HT and FMRFamide receptors that modulate excitability. These results indicate that functional G-protein-coupled receptors for two neuromodulators are distributed differentially along the surface of a presynaptic neuron that forms chemical connections in vitro. This differential distribution of receptors on the presynaptic neuron is regulated by a target and does not require the physical presence of neurons that release the neuromodulators.

Animals↗

PubMed1996

Tetanic stimulation and cyclic adenosine monophosphate regulate segregation of presynaptic inputs on a common postsynaptic target neuron in vitro.

Previous studies indicated that Aplysia sensory neurons (SNs) compete when reestablishing synapses with a motor cell target (L7) in vitro. The competition is characterized by a cell number-dependent decrease in the efficacy of each connection, an increase in the elimination of SN varicosities, a reduction in the formation of new SN varicosities, and the segregation of varicosities of each SN to restricted portions of the target axons. The changes do not require spike activity, since both the SNs and L7 do not fire spontaneously. Here, we examined whether adding activity to SNs during the early stages of synapse formation with stimuli known to evoke facilitatory responses in stable SN-L7 connections--tetanic stimulation or increase in intracellular cyclic adenosine monophosphate (cAMP)--would modulate the intrinsic segregatory process. Tetanic stimulation to one SN increased synapse efficacy and the number of varicosities of the stimulated SNs while reducing the functional changes by the nonstimulated SNs in the same cultures. An increase in the stability of preexisting varicosities contributed to the overall increase in varicosities evoked by tetanus. The functional changes evoked by tetanus were not expressed when the same tetanic stimulation was also given to the other SN, or when L7 was hyperpolarized during the tetanus to the SN. Raising cAMP levels in one SN increased synapse efficacy and the rate of new varicosity formation by the injected SNs without affecting the development of the connections formed by the noninjected SNs. These results suggest that different forms of presynaptic and postsynaptic activities in neurons can regulate specific aspects of the competitive process associated with the fine-tuning of connections formed by converging presynaptic inputs.

Animals↗

PubMed1996

Neuropeptide localization in varicosities of Aplysia sensory neurons is regulated by target and neuromodulators evoking long-term synaptic plasticity.

The synapses between the sensory neuron (SN) and motor neuron of Aplysia undergo long-term functional and structural modulation with appropriate behavioral training or with applications of specific neuromodulators. Expression of molecules within the presynaptic terminals may be regulated in parallel with the changes evoked by the neuromodulators. We examined with immunocytochemical methods whether the level of sensorin, the SN-specific neuropeptide, is modulated in SN varicosities by the location of interaction with the target motor cell L7 and by applications of either 5-HT that evoke long-term facilitation or FMRFamide that evoke long-term depression of Aplysia sensorimotor connections in vitro. A significantly higher proportion of SN varicosities are sensorin positive when they are in contact with the proximal axons of L7 compared to varicosities of the same SNs in contact with distal L7 neurites. Both 5-HT and FMRFamide evoked changes in the efficacy and structure of sensorimotor connections that are accompanied by changes in the frequency of sensorin-positive varicosities contacting the axons of L7. More preexisting SN varicosities are stained after 5-HT, and fewer preexisting SN varicosities are stained after FMRFamide. These results suggest that the postsynaptic target and the neuromodulators not only regulate overall structure but also regulate the level of SN neuropeptide at synaptic sites.

Animals↗

PubMed1996

Development of short-term heterosynaptic facilitation at aplysia sensorimotor synapses in vitro is accompanied by changes in the functional expression of presynaptic serotonin receptors.

1. The sensorimotor synapse of Aplysia expresses various shortlasting changes in synaptic efficacy including homosynaptic depression (HSD) and heterosynaptic facilitation by serotonin (5-HT) either at nondepressed sensory neuron (SN) synaptic connections or at SN synaptic connections first depressed by HSD. We examined the temporal sequence of expression for these three forms of synaptic plasticity as synaptic connections between SN and target motor cell L7 were reestablished and stabilized in cell culture. The same cultures were reexamined at different time points. 2. We found that only HSD and facilitation of nondepressed synapses were expressed at "mature" levels on day 1 in culture, whereas facilitation of depressed connections was significantly weaker on day 1 than the facilitation evoked on day 4. 3. The late expression of 5-HT facilitation of depressed SN synaptic connections was not a result of a reduced capacity of two kinases activated by 5-HT (protein kinase A and protein kinase C) to evoke facilitation. Direct activation of the kinases with either cyclic AMP or phorbol esters evoked the synaptic facilitation both on day 1 and day 4. 4. The late expression of 5-HT facilitation of depressed SN synaptic connections was correlated with the late functional expression of receptors sensitive to 5-HT antagonists cyproheptidine or methiothepin. Both antagonists significantly interfered with 5-HT facilitation on day 4, but both had little effect on 5-HT facilitation of the same cultures examined on day 1. 5. Unlike the properties of SNs in the intact nervous system, both antagonists reduced significantly the excitability changes evoked by 5-HT when the SNs were plated either alone or with target cell L11 that fails to induce synapse formation. When cultured with L7, however, both antagonists evoked little change in 5-HT excitability. In the presence of L7, the SNs expressed the phenotype more typical of SNs in the intact nervous system. 6. The results suggest that target interactions not only influence the formation of chemical connections but they also may regulate the acquisition of specific plastic properties by the presynaptic neuron including the functional expression of receptors for neuromodulators.

Animals↗

PubMed1995

Transient versus persistent functional and structural changes associated with facilitation of Aplysia sensorimotor synapses are second messenger dependent.

Increases in activity of both protein kinase A (PKA) and protein kinase C (PKC) contribute to short-term facilitation of Aplysia sensorimotor synapses evoked by serotonin (5-HT). We report here that increasing levels of cAMP in sensory neurons evokes increases in both synaptic efficacy and in the number of sensory neuron varicosities contacting the major axons of motor cell L7 at intermediate times (3 hr) that persist for 24 hr. Treatment with phorbol esters results in a large transient increase in synaptic efficacy that is accompanied by a large transient increase in the number of sensory neuron varicosities with the newest varicosities most susceptible to elimination. The reversal of the synaptic facilitation and the structural changes does not appear to be the result of long-term inhibitory actions of persistent PKC activation by phorbol esters, since changes in synaptic efficacy can be evoked by additional applications of either phorbol esters or 5-HT. The short-lived changes in structure evoked by phorbol esters occur in preexisting sensory neurites and not by new growth, since increases in PKC activity with phorbol esters lead to reductions in neurite extension and to retractions by sensory neuron growth cones. The action of phorbol esters on growth cone extension is reversible with washout. The results suggest that increases in PKA and PKC activities by 5-HT contribute to short (minutes) and intermediate (hours) forms of facilitation of sensorimotor synapses while increases in PKA activity also mediate long-term (days) maintenance of synaptic facilitation.

Animals↗

PubMed1995

Changes in expression and distribution of Aplysia cell adhesion molecules can influence synapse formation and elimination in vitro.

5-HT or FMRFamide evoke long-lasting changes in the efficacy of sensorimotor (SN-L7) synapses of Aplysia, structural alterations of the presynaptic sensory cell, and cell-specific downregulation in the distribution of the adhesion molecule apCAM. We examined how the cell-specific changes in apCAM might contribute to the formation of new presynaptic varicosities by 5-HT or the elimination of existing presynaptic varicosities by FMRFamide. We report that the formation of new sensory varicosities is directed by the presence of preexisting zones on the motor axon that are enriched for apCAM. Moreover, there was a further enrichment of apCAM levels at existing sensory varicosities contacting the motor axon beginning at 1 hr and lasting 24 hr after treatment with 5-HT. As was found for synapse formation during the early stages of cell-cell interaction, incubation with anti-apCAM mAb blocked the 5-HT-induced long-term changes in synaptic efficacy and the accompanying changes in sensory neuron structure. Long-term synaptic depression with FMRFamide was accompanied by an overall decline of apCAM levels. Treatment with FMRFamide evoked an even greater decline in apCAM levels at sites of sensory varicosities that preceded the structural changes and persisted especially at sites where sensory varicosities are eliminated. These results suggest that neurotransmitters evoke both cell- and site-specific changes in the levels of adhesion molecules that can influence either the formation or the elimination of presynaptic varicosities that accompany long-term heterosynaptic modulation of a behaviorally relevant synaptic connection.

Animals↗

PubMed1994

Locus coeruleus neuronal activity in awake monkeys: relationship to auditory P300-like potentials and spontaneous EEG.

These experiments were designed to test the hypothesis that novel auditory stimuli lead to phasic and/or tonic increases in locus coeruleus (LC) cell firing, which may be a necessary condition for the occurrence of P300 potentials. Event-related potentials (ERPs) and LC unit activity were simultaneously recorded from three awake macaque monkeys exposed to an auditory "oddball" paradigm. Oddball stimuli resulted in probability-sensitive potentials resembling the human P3a component. Twenty-five percent (3/12) of LC units showed small phasic enhancements of LC firing after infrequent but not frequent tones. A comparison between histograms elicited by the two types of stimuli revealed significant effects of stimulus sequence. This pattern suggested a slight activation by rare tones, followed by a brief inhibition of firing in the subsequent trial. These data suggest that changes in LC activity during oddball paradigms are subtle, heterogeneous, and influenced by the subject's level of arousal and vigilance.

Acoustic Stimulation↗

PubMed1994

Pre- and postsynaptic changes mediated by two second messengers contribute to expression of Aplysia long-term heterosynaptic inhibition.

FMRFamide evokes long-term inhibition of the sensorimotor connection of Aplysia that includes structural alterations in the presynaptic sensory cell. FMRFamide also evokes a down-regulation of the adhesion molecule apCAM from the surface of the postsynaptic motor cell L7. We examined the second messenger pathways mediating the long-term actions of FMRFamide on both the pre- and postsynaptic cells and determined whether the activation of each pathway is required for the expression of long-term functional and structural plasticity. Inhibition of the lipoxygenase pathway of arachidonic acid metabolism, but not the cyclooxygenase pathway, blocks the long-term changes in the presynaptic sensory cell evoked by FMRFamide. The down-regulation of apCAM in L7 appears to be mediated by cAMP-dependent activation of protein kinase A. Blocking the cAMP-dependent changes also blocks FMRFamide-induced long-term functional and structural changes. These results suggest that the expression of long-term heterosynaptic inhibition in Aplysia may require concomitant presynaptic and postsynaptic changes, each transduced by specific second messenger systems.

Animals↗

PubMed1994

Decrease in growth cone-neurite fasciculation by sensory or motor cells in vitro accompanies downregulation of Aplysia cell adhesion molecules by neurotransmitters.

Cell adhesion molecules play important roles in axon guidance and synapse formation. Recent studies suggest that the expression of some of these molecules can be regulated either by electrical activity or by specific neurotransmitters. The expression of neural cell adhesion molecule (NCAM)-like molecules in Aplysia, designated apCAM, is downregulated from the surface of sensory neurons by 5-HT, a transmitter known to evoke long-term changes in the structure and function of these neurons. We tested whether the distribution of apCAM on the surface of other neurons can be regulated by treatments with other neurotransmitters known to evoke long-term functional and structural changes in Aplysia neurons, and we examined the consequences of treatments with the neurotransmitters on the pattern of growth cone-neurite interactions. We report that applications of the neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide) that evoke long-term synaptic depression also reduce apCAM expression on the surface of motor cell L7 via a mechanism that appears to be similar to the mechanism mediating the 5-HT-induced change in the sensory cells. Specific treatments that affect apCAM distribution on the surface of their respective cells, 5-HT on sensory cells or FMRFamide on motor cell L7, mimic treatment with monoclonal antibodies against apCAM by evoking a significant reduction in the fasciculation of growth cones with other neurites extending from homologous cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Aplysia cell adhesion molecules and serotonin regulate sensory cell-motor cell interactions during early stages of synapse formation in vitro.

Long-term facilitation of sensorimotor synapses of Aplysia in culture by serotonin (5-HT) is accompanied by two changes: an increase in the number of sensory cell branches and varicosities contacting the major axons of the target motor cell L7, and a downregulation of Aplysia cell adhesion molecules (apCAM) from the surface of the presynaptic sensory cell. We tested the hypothesis that the two changes may be linked; the 5-HT-induced decrease of apCAM levels from sensory neurites may defasciculate sensory neurites from each other and make the surface of the motor axons a more attractive substrate for new growth and synapses. We used developing cultures to examine the relationship of neuritic branching, varicosity formation, and efficacy of the connections formed by sensory cells to levels of apCAM expression on the motor cell. We then determined the consequences of 5-HT applied during the early period of interaction between sensory and motor cells (day 1 or 2 in culture) on the pattern of sensory cell growth and synapse formation. We report that the number of sensory cell branches and varicosities, and the ability of sensory growth cones to fasciculate with L7 axons and form chemical connections correlate with the level of apCAM expression on different regions of L7. Early exposure to 5-HT increased the number of sensory cell branches and varicosities contacting newly regenerated distal neurites of L7 to levels that would normally occur when the sensory neurites interact with the major proximal axons of L7. Treatment with 5-HT also modulated the efficacy of the developing synaptic connections. The change in synapse efficacy was accompanied by an increase in the formation of new sensory varicosities and branches with pioneering growth cones extending on the major axons of L7. The results are consistent with the hypothesis that treatment with 5-HT modulates local differences in the expression of cell adhesion molecules on the surface of the interacting cells making motor neurites more attractive for sensory growth cones, thereby affecting new sensory neuritic growth and synapse formation.

Animals↗