Invagination of presynaptic ribbons in the fly's optic lobe following loss of their target neuron.

In the first optic neuropile of the housefly Musca, photoreceptor terminals innervate fixed clusters of interneurons, one of which is the monopolar cell L2; L2's synapses in turn feed back upon the terminals. We examined the ultrastructure of these feedback synapses following degeneration of their normal targets, the receptor terminals; this was accomplished by photo-ablating the receptor cells after intraretinal injections of sulforhodamine. Even when all the terminals degenerated, their deafferentated target cells, including L2, remained structurally intact for at least 14 d. Despite this lack of obvious trans-synaptic degeneration, L2's synaptic connections did alter. Presynaptic organelles of the feedback synapses, synaptic ribbons and associated synaptic vesicles, soon appeared in L2's cytoplasm, separating from their site of attachment at the presynaptic membrane by invagination. Similar free-floating organelles and vesicles also occurred in another monopolar cell, L4. They were also occasionally encountered in L2, in normal, newly emerged flies at a time when a naturally occurring loss of feedback synapses is greatest. We interpret the process of internalization that forms these floating ribbons to be the first step in synaptic loss which occurs spontaneously, and that the rate is enhanced in L2 when its main synaptic targets, the receptor terminals, degenerate.     

Fly photoreceptor synapses: their development, evolution, and plasticity

Recent studies are reviewed on the synapses of photoreceptor terminals in the first optic neuropile of the flies, Musca and Drosophila. Afferent synaptic contacts are of uniform dimensions; they have a postsynaptic tetrad with a membrane organization of P-face particles, resembling other inhibitory synapses. A distributed population of such contact sites forms progressively during synaptogenesis by the selective, sequential accretion of identified postsynaptic elements at the receptor terminal. The comparative anatomy of this synapse indicates that elements have also been added during its phylogeny from an ancestral dyad. All cells are homologs of those in other species of Diptera. The number of synaptic sites is regulated by both pre- and postsynaptic cells, in proportion to their cell surfaces; an independent size increase in the receptor terminals (procured in the Drosophila mutant gigas) produces an increase in their synaptic population. The number of sites declines with age, however, accompanied by an increase in size of those synaptic sites remaining; this occurs for both afferent and feedback photoreceptor synapses. Lastly, the number of sites changes with visual experience; the frequency of feedback synapses is larger following dark rearing during early adult life than following visual experience.     

Gephyrin expression and clustering affects the size of glutamatergic synaptic contacts

We have recently shown that disrupting the expression and post-synaptic clustering of gephyrin in cultured hippocampal pyramidal cells, by either gephyrin RNAi (RNA interference) or over-expression of a dominant negative gephyrin-enhanced green fluorescent protein (EGFP) fusion protein, leads to decreased number of post-synaptic gephyrin and GABA_A receptor clusters and to reduced GABAergic innervation of these cells. On the other hand, increasing gephyrin expression led to a small increase in the number of gephyrin and GABA_A receptor clusters and to little or no effect on GABAergic innervation. We are now reporting that altering gephyrin expression and clustering affects the size but not the density of glutamatergic synaptic contacts. Knocking down gephyrin with gephyrin RNAi, or preventing gephyrin clustering by over-expression of the dominant negative gephyrin-enhanced green fluorescent protein fusion protein, leads to larger post-synaptic PSD-95 clusters and larger pre-synaptic glutamatergic terminals. On the other hand, over-expression of gephyrin leads to slightly smaller PSD-95 clusters and pre-synaptic glutamatergic terminals. The change in size of PSD-95 clusters were accompanied by a parallel change in the size of NR2-NMDA receptor clusters. It is concluded that the levels of expression and clustering of gephyrin, a protein that concentrates at the post-synaptic complex of the inhibitory synapses, not only has homotypic effects on GABAergic synaptic contacts, but also has heterotypic effects on glutamatergic synaptic contacts. We are proposing that gephyrin is a counterpart of the post-synaptic glutamatergic scaffold protein PSD-95 in regulating the number and/or size of the excitatory and inhibitory synaptic contacts.     

High voltage electron microscopy of the optic neuropile of the housefly,Musca domestica

Synaptic cartridges of the first optic neuropile (lamina ganglionaris) of the housefly were examined by high voltage electron microscopy (HVEM). Stereo pairs (from thick, i.e., 0.25 mum, sections viewed at 1,000 kV) provided a three dimensional representation of cartridge neurons and clearly revealed the lateral spread, bifurcation and some functional associations of Type I (L1, L2) monopolar interneurons. Slightly proximal to cartridge neck level, pairs of retinular (R) axons made contact with each other and it appeared that R processes projected through the cleft between the Type I interneurons. No junctional modifications were seen between contiguous R axon terminals. The speculation was made that functional contact might exist between neighboring R axons prior to their extensive synapses with principal first order interneurons. Such alleged coupling between R axons would account for several electrophysiological findings from other laboratories. Modifications in EM technique applicable for HVEM were detailed. The value of obtaining thick serial sections and the use of the HVEM in expediting three dimensional reconstructions of neuropile were demonstrated.     

Regulation of synaptic frequency: comparison of the effects of hypoinnervation with those of hyperinnervation in the fly's compound eye

At the anterior rim of the first optic neuropile, or lamina, of the housefly's (Musca domestica) compound eye, the terminals of photoreceptors (R) innervate postsynaptic neurons in variable numbers to provide a continuous range of natural hypo- and hyperinnervations. Frequencies of photoreceptor synapses have been measured from quantitative electron microscopy on single sections of the lamina's unit synaptic modules, called cartridges. These are normally innervated by six photoreceptor terminals (6R cartridges). At the lamina's edge hypoinnervated cartridges (2R-5R) are found, whereas hyperinnervated cartridges (7R, 8R) are located at the equator between dorsal and ventral eye halves. In 2R cartridges each presynaptic terminal forms up to 1.5 times the normal, 6R cartridge number of synapses, thereby offsetting the reduced number of terminals and partially conserving the input upon the postsynaptic neurons. Thus the terminals have a reserve synaptogenic capacity never normally revealed. By comparison, terminals in 8R cartridges form about the same numbers of synapses as in "normal" eye regions, so that their postsynaptic neurons have a synaptic input increased by the extra number of terminals. The number of synapses formed between input terminals and target neurons is therefore not fixed but changes as a function of the total receptor terminal complement. The size of a photoreceptor terminal covaries to a certain extent with the number of its presynaptic sites; the spacing density of presynaptic sites over the terminals' surface in a 2R cartridge compared with an 8R cartridge increases far less (only 17%) than the increase in the number of sites (43%). The pair of postsynaptic cell interneurons in each 2R cartridge also shows a decrease in axonal diameter compared with those in 8R cartridges. Thus both the pre- and postsynaptic cells show size changes correlated with changes in their synaptic engagement.     

Pre- and post-synaptic structures in insect CNS: intramembranous features and sites of alpha-bungarotoxin binding

The central neuropile of thoracic ganglia in the central nervous system (CNS) of the cockroach Periplaneta americana contains synapses with characteristic pre- and post-synaptic membrane specializations and associated structures. These include dense pre-synaptic T-bars surrounded by synaptic vesicles, together with post-synaptic densities of varying electron opacity. Exocytotic release of synaptic vesicles is observed only rarely near presynaptic densities, but coated pits are seen at variable distances from them, and may be involved in membrane retrieval. After freeze-fracture, paralinear arrays of intramembranous articles (IMPs) are detected on the P face of many presynaptic terminals, with associated dimples indicative of vesicular release. The E face of these membranes exhibits protuberances complementary to the P face dimples, as well as scattered larger IMPs. Post-synaptic membranes possess dense IMP aggregates on the P face, some of which may represent receptor molecules. Electrophysiological studies with biotinylated alpha-bungarotoxin reveal that biotinylation does not inhibit the pharmacological effectiveness of the toxin in blocking acetylcholine receptors on an identified motoneurone in the metathoracic ganglion. Preliminary thin section ultrastructural analysis of this tissue post-treated with avidin-HRP or avidin-ferritin indicates that alpha-bungarotoxin-binding sites are localized at certain synapses in these insect thoracic ganglia.     

Acetylcholine receptors in regenerating muscle accumulate at original synaptic sites in the absence of the nerve

We examined the role of nerve terminals in organizing acetylcholine receptors on regenerating skeletal-muscle fibers. When muscle fibers are damaged, they degenerate and are phagocytized, but their basal lamina sheaths survive. New myofibers form within the original basal lamina sheaths, and they become innervated precisely at the original synaptic sites on the sheaths. After denervating and damaging muscle, we allowed myofibers to regenerate but deliberately prevented reinnervation. The distribution of acetylcholine receptors on regenerating myofibers was determined by histological methods, using [125I] alpha-bungarotoxin or horseradish peroxidase-alpha-bungarotoxin; original synaptic sites on the basal lamina sheaths were marked by cholinesterase stain. By one month after damage to the muscle, the new myofibers have accumulations of acetylcholine receptors that are selectively localized to the original synaptic sites. The density of the receptors at these sites is the same as at normal neuromuscular junctions. Folds in the myofiber surface resembling junctional folds at normal neuromuscular junctions also occur at original synaptic sites in the absence of nerve terminals. Our results demonstrate that the biochemical and structural organization of the subsynaptic membrane in regenerating muscle is directed by structures that remain at synaptic sites after removal of the nerve.     

Cell recognition during synaptogenesis is revealed after temperature-shock-induced perturbations in the developing fly's optic lamina

Houseflies (Musca domestica) were exposed to pulses of heat (1 h) or cold (several hours) during early pupal life, and the effects were investigated on the development of the first optic neuropile, or lamina, of the visual system. The treatments were designed to perturb the cellular or ganization of the cartridges, the unit synaptic structures of the lamina, so as to provide novel synaptic opportunities amongst the normally fixed composition of these modules, thereby testing the preferences of their component cells during synaptogenesis. Various abnormalities were identified, but these were not always consistent between flies: retinal abnormalities included the loss and fusion of rhabdomeres, especially of the central cells of the ommatidium, whereas in the lamina low frequencies of abnormal cartridges were found. These included seven that were studied with serial sections, which instead of the normal pair of L1 and L2 monopolar interneurons had supernumerary cells of this type. The normal pairing of L1 and L2 at postsynaptic sites of receptor terminal tetrad synapses was preserved in these cases, the cells eschewing pairings of homologous L1/L1 or L2/L2 partners. This meant that more than one L1 could pair with a single L2 and vice versa, even at the same terminal, and appeared to do so opportunistically on the basis of proximity, with cells closer to each other pairing more frequently. Thus the cells behave during synaptogenesis as if they recognize other cells only as cell types (receptor, L1 or L2) and not as individual cells. © 1993 John Wiley & Sons, Inc.     

Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites

Axons regenerate to reinnervate denervated skeletal muscle fibers precisely at original synaptic sites, and they differentiate into nerve terminals where they contact muscle fibers. The aim of this study was to determine the location of factors that influence the growth and differentiation of the regenerating axons. We damaged and denervated frog muscles, causing myofibers and nerve terminals to degenerate, and then irradiated the animals to prevent regeneration of myofibers. The sheath of basal lamina (BL) that surrounds each myofiber survives these treatments, and original synaptic sites on BL can be recognized by several histological criteria after nerve terminals and muscle cells have been completely removed. Axons regenerate into the region of damage within 2 wk. They contact surviving BL almost exclusively at original synaptic sites; thus, factors that guide the axon's growth are present at synaptic sites and stably maintained outside of the myofiber. Portions of axons that contact the BL acquire active zones and accumulations of synaptic vesicles; thus by morphological criteria they differentiate into nerve terminals even though their postsynaptic targets, the myofibers, are absent. Within the terminals, the synaptic organelles line up opposite periodic specializations in the myofiber's BL, demonstrating that components associated with the BL play a role in organizing the differentiation of the nerve terminal.     

The Organization of the lamina ganglionaris of the prawn,Pandalus borealis (Kröyer)

The Lamina ganglionaris (first optic neuropile) of the decapod crustacean Pandalus borealis has its optic cartridges (synaptic compartments) arranged in horizontal rows. Each optic cartridge contains seven receptor axon terminals and the branching axis fibres of five monopolar second order neurons. Four types of monopolar neurons are classified. Their cell bodies are arranged in two layers. The inner layer contains the cell bodies of exclusively one of these types, and each cartridge is invaded by two neurons of this neuron type (type M 1:a and M 1:b). The outer layer contains the cell bodies of the remaining three types (M 2, M3 and M4). One gives rise to a large radially branched axis fibre in the centre of the cartridge. The other two have wide branches which may make inter-cartridge contacts, one proximally and the other distally in the plexiform layer, which is clearly bistratified. The receptor axons terminate in two levels corresponding to these strata. Two sets of tangenital fibres form networks in the proximal and the mid-portion of the lamina. Both networks have fibres with primary branches in the vertical plane and secondary branches in the horizontal plane. The fibres of the networks are derived from axons that pass from the second optic neuropile, the medulla externa.     

Involvement of glial cells in rhythmic size changes in neurons of the housefly's visual system

In the housefly's first optic neuropile, or lamina, the axons of two classes of monopolar cell interneurons, L1 and L2, exhibit a daily rhythm of size changes: swelling during the day, and shrinking by night. At least for the L2 cells this rhythm is circadian. Moreover, epithelial glial cells that enwrap each lamina cartridge, its monopolar cell axons, and their surrounding crown of input photoreceptor terminals also change size, but in the opposite direction to the changes in L1 and L2-swelling by night and shrinking by day. The rhythmic changes in glia indicate the possible involvement of these cells in the lamina's circadian system. To examine their role in regulating the rhythmic changes of L1 and L2's axon sizes we have injected three chemicals into the haemolymph of the fly's head: fluorocitrate (FL) and iodoacetate (IAA), which affect the metabolism of glial cells, and octanol (OC), which closes gap junction channels. All chemicals exerted an effect on L1 and L2, which depended on the time of injection, the drug concentration, and the postinjection times at which we examined the fly's brains. Moreover, day/night changes in the axon sizes of L1 and L2 were increased in FL- and IAA-treated flies, indicating that glial cells may normally inhibit these changes by regulating the sizes of L1 and L2's axons during the day and night. In turn, lack of a day/night rhythm in L1 and L2 after OC injections shows that the rhythm's persistence depends on communication between the lamina cells through gap junction channels.     

Feedback network controls photoreceptor output at the layer of first visual synapses in Drosophila

At the layer of first visual synapses, information from photoreceptors is processed and transmitted towards the brain. In fly compound eye, output from photoreceptors (R1-R6) that share the same visual field is pooled and transmitted via histaminergic synapses to two classes of interneuron, large monopolar cells (LMCs) and amacrine cells (ACs). The interneurons also feed back to photoreceptor terminals via numerous ligand-gated synapses, yet the significance of these connections has remained a mystery. We investigated the role of feedback synapses by comparing intracellular responses of photoreceptors and LMCs in wild-type Drosophila and in synaptic mutants, to light and current pulses and to naturalistic light stimuli. The recordings were further subjected to rigorous statistical and information-theoretical analysis. We show that the feedback synapses form a negative feedback loop that controls the speed and amplitude of photoreceptor responses and hence the quality of the transmitted signals. These results highlight the benefits of feedback synapses for neural information processing, and suggest that similar coding strategies could be used in other nervous systems.     

Pre- and post-synaptic structures in insect CNS: Intramembranous features and sites of α-bungarotoxin binding

The central neuropile of thoracic ganglia in the central nervous system (CNS) of the cockroach Periplaneta americana contains synapses with characteristic pre- and post-synaptic membrane specializations and associated structures. These include dense pre-synaptic T-bars surrounded by synaptic vesicles, together with post-synaptic densities of varying electron opacity. Exocytotic release of synaptic vesicles is observed only rarely near presynaptic densities, but coated pits are seen at variable distances from them, and may be involved in membrane retrieval. After freeze-fracture, paralinear arrays of intramembranous particles (IMPs) are detected on the P face of many presynaptic terminals, with associated dimples indicative of vesicular release. The E face of these membranes exhibits protuberances complementary to the P face dimples, as well as scattered larger IMPs. Post-synaptic membranes possess dense IMP aggregates on the P face, some of which may represent receptor molecules. Electrophysiological studies with biotinylated α-bungarotoxin reveal that biotinylation does not inhibit the pharmacological effectiveness of the toxin in blocking acetylcholine receptors on an identified motoneurone in the metathoracic ganglion. Preliminary thin section ultrastructural analysis of this tissue post-treated with avidin-HRP or avidin-ferritin indicates that α-bungarotoxin-binding sites are localized at certain synapses in these insect thoracic ganglia.     

Subcellular compartment-specific molecular diversity of pre- and post-synaptic GABAB-activated GIRK channels in Purkinje cells

Activation of G protein-gated inwardly-rectifying K⁺ (GIRK or Kir3) channels by metabotropic gamma-aminobutyric acid (B) (GABA_B) receptors is an essential signalling pathway controlling neuronal excitability and synaptic transmission in the brain. To investigate the relationship between GIRK channel subunits and GABA_B receptors in cerebellar Purkinje cells at post- and pre-synaptic sites, we used biochemical, functional and immunohistochemical techniques. Co-immunoprecipitation analysis demonstrated that GIRK subunits are co-assembled with GABA_B receptors in the cerebellum. Immunoelectron microscopy showed that the subunit composition of GIRK channels in Purkinje cell spines is compartment-dependent. Thus, at extrasynaptic sites GIRK channels are formed by GIRK1/GIRK2/GIRK3, post-synaptic densities contain GIRK2/GIRK3 and dendritic shafts contain GIRK1/GIRK3. The post-synaptic association of GIRK subunits with GABA_B receptors in Purkinje cells is supported by the subcellular regulation of the ion channel and the receptor in mutant mice. At pre-synaptic sites, GIRK channels localized to parallel fibre terminals are formed by GIRK1/GIRK2/GIRK3 and co-localize with GABA_B receptors. Consistent with this morphological evidence we demonstrate their functional interaction at axon terminals in the cerebellum by showing that GIRK channels play a role in the inhibition of glutamate release by GABA_B receptors. The association of GIRK channels and GABA_B receptors with excitatory synapses at both post- and pre-synaptic sites indicates their intimate involvement in the modulation of glutamatergic neurotransmission in the cerebellum.     

Interneurons: an electron microscopic study of the cat's hippocampal formation, II.

The ultrastructure of interneurons was studied in the cat and it was found to differ from that of the pyramidal and granule cells. The size, shape and topographic situation of the cell body of interneurons were the criteria for approaching their identification with the cells found in Golgi material. Some interneuron dendrites are also described. The varicose and spindle-shaped dendritic profiles belonging to interneurons are different in size. In Golgi material the interneurons have beaded (varicose) or spindle-shaped dendrites. The arrangement of synaptic terminals on the interneuron dendritic surface seems to be their characteristic feature.     

Assessing the Role of Cell-Surface Molecules in Central Synaptogenesis in the Drosophila Visual System

A hallmark of the central nervous system is its spatial and functional organization in synaptic layers. During neuronal development, axons form transient contacts with potential post-synaptic elements and establish synapses with appropriate partners at specific layers. These processes are regulated by synaptic cell-adhesion molecules. In the Drosophila visual system, R7 and R8 photoreceptor subtypes target distinct layers and form en passant pre-synaptic terminals at stereotypic loci of the axonal shaft. A leucine-rich repeat transmembrane protein, Capricious (Caps), is known to be selectively expressed in R8 axons and their recipient layer, which led to the attractive hypothesis that Caps mediates R8 synaptic specificity by homophilic adhesion. Contradicting this assumption, our results indicate that Caps does not have a prominent role in synaptic-layer targeting and synapse formation in Drosophila photoreceptors, and that the specific recognition of the R8 target layer does not involve Caps homophilic axon-target interactions. We generated flies that express a tagged synaptic marker to evaluate the presence and localization of synapses in R7 and R8 photoreceptors. These genetic tools were used to assess how the synaptic profile is affected when axons are forced to target abnormal layers by expressing axon guidance molecules. When R7 axons were mistargeted to the R8-recipient layer, R7s either maintained an R7-like synaptic profile or acquired a similar profile to r8s depending on the overexpressed protein. When R7 axons were redirected to a more superficial medulla layer, the number of presynaptic terminals was reduced. These results indicate that cell-surface molecules are able to dictate synapse loci by changing the axon terminal identity in a partially cell-autonomous manner, but that presynapse formation at specific sites also requires complex interactions between pre- and post-synaptic elements.     

Cerebral-buccal pathways in Aplysia californica: synaptic connections, cooperative interneuronal effects and feedback during buccal motor programs

Ingestion of seaweed by Aplysia is in part mediated by cerebral-buccal interneurons that drive rhythmic motor output from the buccal ganglia and in some cases cerebral-buccal interneurons act as members of the feeding central pattern generator. Here we document cooperative interactions between cerebral-buccal interneuron 2 and cerebral-buccal interneuron 12, characterize synaptic input to cerebral-buccal interneuron 2 and cerebral-buccal interneuron 12 from buccal peripheral nerve 2,3, describe a synaptic connection between cerebral-buccal interneuron 1 and buccal neuron B34, further characterize connections made by cerebral-buccal interneurons 2 and -12 with B34 and B61/62, and describe a novel, inhibitory connection made by cerebral-buccal interneuron 2 with a buccal neuron. When cerebral-buccal interneurons 2 and 12 were driven synchronously at low frequencies, ingestion-like buccal motor programs were elicited, and if either was driven alone, indirect synaptic input was recruited in the other cerebral-buccal interneuron. Stimulation of BN2,3 recruited both ingestion and rejection-like motor programs without firing in cerebral-buccal interneurons 2 or 12. During motor programs elicited by cerebral-buccal interneurons 2 or 12, high-voltage stimulation of BN2,3 inhibited firing in both cerebral-buccal interneurons. Our results suggest that cerebral-buccal interneurons 2 and 12 use cooperative interactions to modulate buccal motor programs, yet firing in cerebral-buccal interneurons 2 or 12 is not necessary for recruiting motor programs by buccal peripheral nerve BN2,3, even in preparations with intact cerebral-buccal pathways.     

The superposition eye of Cloeon dipterum: The organization of the lamina ganglionaris

Summary The lamina ganglionaris of the superposition eye of Cloeon dipterum is composed of separate optic cartridges arranged in a hexagonal pattern. Each optic cartridge consists of one central, radially branched monopolar cell (Li) surrounded by a crown of seven retinula cell terminals and two more unilaterally branched monopolar cells (La1/La2) situated close together outside the cartridge. Projections to neighbouring cartridges have not been observed.In most cases, synaptic contacts could be seen between a presynaptic retinula cell and more than two other postsynaptic profiles, which belong to monopolar cells or sometimes to glial cells.Seven retinula cell fibers of one ommatidium pass in a bundle through the basement membrane, run into their respective cartridges without changing orientation and terminate at approximately equal levels in the lamina. Long visual fibers with endings in the medulla are not visible in the superposition eye lamina, but are present in the lateral apposition eye. The relationship between the behaviour of the animal, optic mechanisms of the superposition eye and the structure of the lamina is discussed.     

Pre-synaptic and post-synaptic localization of EphA4 and EphB2 in adult mouse forebrain

The ephrin receptors EphA4 and EphB2 have been implicated in synaptogenesis and long-term potentiation in the cerebral cortex and hippocampus, where they are generally viewed as post-synaptic receptors. To determine the precise distribution of EphA4 and EphB2 in mature brain synapses, we used subcellular fractionation and electron microscopy to examine the adult mouse forebrain/midbrain. EphA4 and EphB2 were both enriched in microsomes and synaptosomes. In synaptosomes, they were present in the membrane and the synaptic vesicle fractions. While EphA4 was tightly associated with PSD-95-enriched post-synaptic density fractions, EphB2 was easily extracted with detergents. In contrast, both receptors were found in the pre-synaptic active zone fraction. By electron microscopy, EphA4 was mainly detected in axon terminals, whereas EphB2 was more frequently detected in large dendritic shafts, in the hippocampus and cerebral cortex. However, in the ventrobasal thalamus, EphB2 was detected most frequently in axon terminals and thin dendritic shafts. The localization of EphA4 and EphB2 in multiple compartments of neurons and synaptic junctions suggests that they interact with several distinct scaffolding proteins and play diverse roles at synapses.     

Short-Term Synaptic Plasticity Orchestrates the Response of Pyramidal Cells and Interneurons to Population Bursts

The synaptic drive from neuronal populations varies considerably over short time scales. Such changes in the pre-synaptic rate trigger many temporal processes absent under steady-state conditions. This paper examines the differential impact of pyramidal cell population bursts on post-synaptic pyramidal cells receiving depressing synapses, and on a class of interneuron that receives facilitating synapses. In experiment a significant shift of the order of one hundred milliseconds is seen between the response of these two cell classes to the same population burst. It is demonstrated here that such a temporal differentiation of the response can be explained by the synaptic and membrane properties without recourse to elaborate cortical wiring schemes. Experimental data is first used to construct models of the two types of dynamic synaptic response. A population-based approach is then followed to examine analytically the temporal synaptic filtering effects of the population burst for the two post-synaptic targets. The peak-to-peak delays seen in experiment can be captured by the model for experimentally realistic parameter ranges. It is further shown that the temporal separation of the response is communicated in the outgoing action potentials of the two post-synaptic cells: pyramidal cells fire at the beginning of the burst and the class of interneuron receiving facilitating synapses fires at the end of the burst. The functional role of such delays in the temporal organisation of activity in the cortical microcircuit is discussed.