Fast recruitment of recurrent inhibition in the cat visual cortex

Neurons of the same column in L4 of the cat visual cortex are likely to share the same sensory input from the same region of the visual field. Using visually-guided patch clamp recordings we investigated the biophysical properties of the synapses of neighboring layer 4 neurons. We recorded synaptic connections between all types of excitatory and inhibitory neurons in L4. The E-E, E-I, and I-E connections had moderate CVs and failure rates. However, E-I connections had larger amplitudes, faster rise-times, and shorter latencies. Identification of the sites of putative synaptic contacts together with compartmental simulations on 3D reconstructed cells, suggested that E-I synapses tended to be located on proximal dendritic branches, which would explain their larger EPSP amplitudes and faster kinetics. Excitatory and inhibitory synapses were located at the same distance on distal dendrites of excitatory neurons. We hypothesize that this co-localization and the fast recruitment of local inhibition provides an efficient means of modulating excitation in a precisely timed way.     

Positional information determines the anatomy and synaptic specificity of cockroach filiform hair afferents using independent mechanisms

Summary Mutant first instar cockroaches (Periplaneta americana) with supernumerary filiform hair sensilla on their cerci were used to study the effects of cell body position on axonal morphology and synaptic connections. The wild-type cercus has two hairs, one lateral (L) and the other medial (M), each with an underlying sensory neuron. Silver-intensified cobalt fills show that the supernumerary lateral neuron (SIN) in the mutant has the same shape of arborization as L, and electrophysiological recording shows that it forms synaptic connections with the same subset of giant interneurons (GIs) as L in the terminal ganglion: GI3 and GI6. The supernumerary medial neuron (SuM) has the same axonal morphology as M and synapses with the same GIs as does M: ipsilateral GIs 1 and 2 and contralateral GIs 1, 2, 3, 5 and 6. In 0.1% of approximately 8000 animals screened, a supernumerary hair arose on the cereal midline (C hair). The C neuron sends its axon to the CNS in the same branch of the cereal nerve as the L and SIN, and has a similar arborization. However, the C neuron forms synapses with the same GIs as do M and SuM. Electron microscopy of horseradish peroxidase-injected neurons was used to confirm that the C afferent forms a monosynaptic connection to GI2. It was concluded that the position of the sensory neuron cell body does control its axonal morphology and synaptic connectivity, but that these characteristics are produced by independent mechanisms.Abbreviations GI giant interneuron - L lateral - M medial - SI Space Invader - SuM supernumerary medial - C cereal midline     

Ectopic sensory neurons in mutant cockroaches compete with normal cells for central targets.

The cercus of the first instar cockroach, Periplaneta americana, bears two filiform hairs, lateral (L) and medial (M), each of which is innervated by a single sensory neuron. These project into the terminal ganglion of the CNS where they make synaptic connections with a number of ascending interneurons. We have discovered mutant animals that have more hairs on the cercus; the most typical phenotype, called "Space Invader" (SI), has an extra filiform hair in a proximo-lateral position on one of the cerci. The afferent neuron of this supernumerary hair (SIN) "invades the space" occupied by L in the CNS and makes similar synaptic connections to giant interneurons (GIs). SIN and L compete for these synaptic targets: the size of the L EPSP in a target interneuron GI3 is significantly reduced in the presence of SIN. Morphometric analysis of the L afferent in the presence or absence of SIN shows no anatomical concomitant of competition. Ablation of L afferent allows SIN to increase the size of its synaptic input to GI3. Less frequently in the mutant population, we find animals with a supernumerary medical (SuM) sensillum. Its afferent projects to the same neuropilar region as the M afferent, makes the same set of synaptic connections to GIs, and competes with M for these synaptic targets. The study of these competitive interactions between identified afferents and identified target interneurons reveals some of the dynamic processes that go on in normal development to shape the nervous system.     

Patterns of monosynaptic input to the giant interneurons 1–3 in the cereal system of the adult cockroach

1. The cerci of the cockroach Periplaneta americana bear filiform hair mechanoreceptors that are arranged in segmentally repeated rows and longitudinal columns. The monosynaptic connections between receptors of the same column or row and the 3 largest giant interneurons (GIs) were compared using the oil-gap single fibre technique.
2. For many columns, the synaptic efficacy of the afferents decreased gradually from the base to the tip of the cercus, but columns with an inverted gradient or without any gradient were also observed. On the ipsilateral side (relative to the GI axon), the inverted gradients were exclusively found for columns with short proximal hairs. For one column (d) and GI3, the ipsilateral and contralateral gradients were opposite.
3. Monosynaptic EPSPs evoked by stimulating different receptors of the same segment (segment 3) were of very different amplitudes, which partially account for the directional sensitivity of the GIs. Differences in the location, shape and size of the afferent terminals were not sufficient to explain these differences in connection strength.
4. No correlation was found between the size of the EPSPs produced by a sensory neuron and the length of its associated hair.

     

Electrical advantages of dendritic spines

Many neurons receive excitatory glutamatergic input almost exclusively onto dendritic spines. In the absence of spines, the amplitudes and kinetics of excitatory postsynaptic potentials (EPSPs) at the site of synaptic input are highly variable and depend on dendritic location. We hypothesized that dendritic spines standardize the local geometry at the site of synaptic input, thereby reducing location-dependent variability of local EPSP properties. We tested this hypothesis using computational models of simplified and morphologically realistic spiny neurons that allow direct comparison of EPSPs generated on spine heads with EPSPs generated on dendritic shafts at the same dendritic locations. In all morphologies tested, spines greatly reduced location-dependent variability of local EPSP amplitude and kinetics, while having minimal impact on EPSPs measured at the soma. Spine-dependent standardization of local EPSP properties persisted across a range of physiologically relevant spine neck resistances, and in models with variable neck resistances. By reducing the variability of local EPSPs, spines standardized synaptic activation of NMDA receptors and voltage-gated calcium channels. Furthermore, spines enhanced activation of NMDA receptors and facilitated the generation of NMDA spikes and axonal action potentials in response to synaptic input. Finally, we show that dynamic regulation of spine neck geometry can preserve local EPSP properties following plasticity-driven changes in synaptic strength, but is inefficient in modifying the amplitude of EPSPs in other cellular compartments. These observations suggest that one function of dendritic spines is to standardize local EPSP properties throughout the dendritic tree, thereby allowing neurons to use similar voltage-sensitive postsynaptic mechanisms at all dendritic locations.     

Identified target motor neuron regulates neurite outgrowth and synapse formation of aplysia sensory neurons in vitro

To determine the influence that an appropriate target cell has on the axonal structure of a presynaptic neuron in vivo, we examined the morphologies of individual Aplysia sensory neurons in dissociated cell culture in the presence or absence of identified target motor neurons. We find that an appropriate target, the motor cell L7, regulates the morphological differentiation of the presynaptic sensory neurons in two ways: the target induces the axons of the sensory neurons to develop a more elaborate structure and to form active zones, and the target guides the outgrowth of the sensory neurons. The influence of the appropriate target, L7, on the morphological differentiation of sensory neurons appears to be related to the formation of chemical synaptic connections between the sensory neurons and L7, since sensory neurons co-cultured with an inappropriate target motor neuron do not exhibit a comparable elaboration of their axonal processes.     

The heterogeneity of the excitatory synaptic inputs in the spinal motor neurons of the frog Rana ridibunda

The synaptic responses induced in motoneurones by the stimulations of the dorsal root (DR), single afferent fibres and reticular formation (RF) were intracellularly recorded in the isolated frog spinal cord. It was shown that argiopine (the selective blocker of glutamate receptors of non-NMDA type) in concentrations ranging from 3.10(-7) to 1.10(-5) M effectively suppressed the di- and polysynaptic, but not the monosynaptic components of EPSP's induced by DR stimulation. The initial reaction to argiopine consisted of the increase of this monosynaptic component of EPSP. In the same concentrations range, argiopine reduced both mono- and polysynaptic EPSP, evoked by RF stimulation. 2-amino-phosphonovaleric acid (1.10(-4) M) did not affect, whereas the kinurenate (1--2.10(-3) M) completely blocked the amplitude of all kinds of synaptic responses. The various effects of argiopine on the responses induced by microstimulation of presynaptic nerve terminals were observed. The data obtained speak in favour of heterogeneity of monosynaptic excitatory inputs in the motoneurones of frog spinal cord. Being the glutamatergic by nature, the inputs differ in the properties of postsynaptic receptors. All of these receptors concerning to non NMDA-type can be divided to argiopine-sensitive and argiopine-resistant. The first seem to be involved in the monosynaptic connections of RF and the second--in those of primary afferents with motoneurones.     

Multiple clusters of release sites formed by individual thalamic afferents onto cortical interneurons ensure reliable transmission

Thalamic afferents supply the cortex with sensory information by contacting both excitatory neurons and inhibitory interneurons. Interestingly, thalamic contacts with interneurons constitute such a powerful synapse that even one afferent can fire interneurons, thereby driving feedforward inhibition. However, the spatial representation of this potent synapse on interneuron dendrites is poorly understood. Using Ca imaging and electron microscopy we show that an individual thalamic afferent forms multiple contacts with the interneuronal proximal dendritic arbor, preferentially near branch points. More contacts are correlated with larger amplitude synaptic responses. Each contact, consisting of a single bouton, can release up to seven vesicles simultaneously, resulting in graded and reliable Ca transients. Computational modeling indicates that the release of multiple vesicles at each contact minimally reduces the efficiency of the thalamic afferent in exciting the interneuron. This strategy preserves the spatial representation of thalamocortical inputs across the dendritic arbor over a wide range of release conditions.     

Local gating of information processing through the thalamus

Inhibitory sculpting of afferent signals in the thalamus is exerted by two types of neurons using gamma-amino butyric acid (GABA) as neurotransmitter. Of them, local-circuit neurons exert their functions via two outputs: axons and presynaptic dendrites. In this issue of Neuron, Govindaiah and Cox reveal that synaptic activation of metabotropic glutamate receptors selectively increases the output of presynaptic dendrites of local interneurons in rat visual thalamus, without affecting the axonal output.     

Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic input

As the nervous system develops, there is an inherent variability in the connections formed between differentiating neurons. Despite this variability, neural circuits form that are functional and remarkably robust. One way in which neurons deal with variability in their inputs is through compensatory, homeostatic changes in their electrical properties. Here, we show that neurons also make compensatory adjustments to their structure. We analysed the development of dendrites on an identified central neuron (aCC) in the late Drosophila embryo at the stage when it receives its first connections and first becomes electrically active. At the same time, we charted the distribution of presynaptic sites on the developing postsynaptic arbor. Genetic manipulations of the presynaptic partners demonstrate that the postsynaptic dendritic arbor adjusts its growth to compensate for changes in the activity and density of synaptic sites. Blocking the synthesis or evoked release of presynaptic neurotransmitter results in greater dendritic extension. Conversely, an increase in the density of presynaptic release sites induces a reduction in the extent of the dendritic arbor. These growth adjustments occur locally in the arbor and are the result of the promotion or inhibition of growth of neurites in the proximity of presynaptic sites. We provide evidence that suggest a role for the postsynaptic activity state of protein kinase A in mediating this structural adjustment, which modifies dendritic growth in response to synaptic activity. These findings suggest that the dendritic arbor, at least during early stages of connectivity, behaves as a homeostatic device that adjusts its size and geometry to the level and the distribution of input received. The growing arbor thus counterbalances naturally occurring variations in synaptic density and activity so as to ensure that an appropriate level of input is achieved.     

Specification of synaptic connections between sensory and motor neurons in the developing spinal cord

Experimental studies of mechanisms underlying the specification of synaptic connections in the monosynaptic stretch reflex of frogs and chicks are described. Sensory neurons innervating the triceps brachii muscles of bullfrogs are born throughout the period of sensory neurogenesis and do not appear to be related clonally. Instead, the peripheral targets of these sensory neurons play a major role in determining their central connections with motoneurons. Developing thoracic sensory neurons made to project to novel targets in the forelimb project into the brachial spinal cord, which they normally never do. Moreover, these foreign sensory neurons make monosynaptic excitatory connections with the now functionally appropriate brachial motoneurons. Normal patterns of neuronal activity are not necessary for the formation of specific central connections. Neuromuscular blockade of developing chick embryos with curare during the period of synaptogenesis still results in the formation of correct sensory-motor connections. Competitive interactions among the afferent fibers also do not seem to be important in this process. When the number of sensory neurons projecting to the forelimb is drastically reduced during development, each afferent still makes central connections of the same strength and specificity as normal. These results are discussed with reference to the development of retinal ganglion cells and their projections to the brain. Although many aspects of the two systems are similar, patterned neural activity appears to play a much more important role in the development of the visual pathway than in the spinal reflex pathway described here.     

Ultrastructural organization of the synapses in ganglia of the hen intestinal nerve under various conditions of its activity

The interneuronal connections in ganglia of the caudal part of the hen intestinal nerve of Remak are presented as axodendritic and axosomatic synapses and symmetric axo-axonal, dendro-dendritic and axodendritic contacts, often forming complicated complexes. Under conditions of preliminary decentralization or under certain disturbances of nervous connections with the intestine, a part of synapses remains, and a part of them degenerates, this demonstrates participation of peripheral afferent neurons in formation of the synaptic apparatus of the ganglia mentioned. The axonal terminals differentiate by composition of the synaptic vesicles: some contain mainly light agranular vesicles, others--a large amount of granular ones. The characteristic peculiarities of the hen intestinal nerve ganglia, in contrast to analogous mammalian ganglia, are abundant axosomatic synapses in some neurons, and presynaptic terminals, containing a large number of granular vesicles.     

A major role for intracortical circuits in the strength and tuning of odor-evoked excitation in olfactory cortex

In primary sensory cortices, there are two main sources of excitation: afferent sensory input relayed from the periphery and recurrent intracortical input. Untangling the functional roles of these two excitatory pathways is fundamental for understanding how cortical neurons process sensory stimuli. Odor representations in the primary olfactory (piriform) cortex depend on excitatory sensory afferents from the olfactory bulb. However, piriform cortex pyramidal cells also receive dense intracortical excitatory connections, and the relative contribution of these two pathways to odor responses is unclear. Using a combination of in vivo whole-cell voltage-clamp recording and selective synaptic silencing, we show that the recruitment of intracortical input, rather than olfactory bulb input, largely determines the strength of odor-evoked excitatory synaptic transmission in rat piriform cortical neurons. Furthermore, we find that intracortical synapses dominate odor-evoked excitatory transmission in broadly tuned neurons, whereas bulbar synapses dominate excitatory synaptic responses in more narrowly tuned neurons.     

Angiotensin potentiates excitatory sensory synaptic transmission to medial solitary tract nucleus neurons

Femtomole doses of angiotensin (ANG) II microinjected into nucleus tractus solitarii (nTS) decrease blood pressure and heart rate, mimicking activation of the baroreflex, whereas higher doses depress this reflex. ANG II might generate cardioinhibitory responses by augmenting cardiovascular afferent synaptic transmission onto nTS neurons. Intracellular recordings were obtained from 99 dorsal medial nTS region neurons in rat medulla horizontal slices to investigate whether ANG II modulated short-latency excitatory postsynaptic potentials (EPSPs) evoked by solitary tract (TS) stimulation. ANG II (200 fmol) increased TS-evoked EPSP amplitudes 20-200% with minimal membrane depolarization in 12 neurons excited by ANG II and glutamate, but not substance P (group A). Blockade of non-N-methyl-d-aspartate receptors eliminated TS-evoked EPSPs and responses to ANG II. ANG II did not alter TS-evoked EPSPs in 14 other neurons depolarized substantially by ANG II and substance P (group B). ANG II appeared to selectively augment presynaptic sensory transmission in one class of nTS neurons but had only postsynaptic effects on another group of cells. Thus ANG II is likely to modulate cardiovascular function by more than one nTS neuronal pathway.     

Target-dependent morphological segregation of Aplysia sensory outgrowth in vitro.

The adult nervous system is characterized by partial or complete morphological segregation of terminals from different afferent neurons innervating the same postsynaptic target. This segregation is thought to result, in part, from competition between the afferent terminals. To explore the role of the target cell in the spatial distribution of presynaptic inputs, the sensory neurons of Aplysia were cultured either with or without a common target motor neuron. In the presence of a common target, the outgrowth from two different sensory neurons tends to occupy separate postsynaptic regions. When cultured without a target motor neuron, processes from different sensory neurons do not segregate, but rather grow freely along one another. Thus, morphological segregation of sensory outgrowth requires interaction with a target neuron and may reflect competition between presynaptic terminals for a limited number of synaptic sites on the motor neuron, or for a postsynaptic trophic factor.     

Long-term potentiation in the neurons of the edible snail

A brief high-frequency stimulation of the anal nerve of the isolated nerve ring of snail Helix induced a pronounced increase in the amplitude of EPSPs, evoked in identified neurons of left parietal and visceral ganglions by low frequency (once in 5 min) stimulation of the same nerve. The amplitude of EPSP returned to the control level 30-120 min after tetanization. We called this effect long-term potentiation. A brief application of serotonin (10 microM) in the majority of neurons also induced lasting either 15-30 min or more than 2 hours facilitation of EPSP, evoked by anal nerve stimulation. Intracellular cAMP injections, being without effect on EPSP amplitude in many neurons, in certain neurons caused an increase in EPSP amplitude, lasting up to 30 min. It is suggested that the 3 factors shown to increase synaptic efficiency in molluscan neurons may have common mechanisms of action.     

Cholinergic neurotransmission from mechanosensory afferents to giant interneurons in the terminal abdominal ganglion of the cricket Gryllus bimaculatus

Crickets respond to air currents with quick avoidance behavior. The terminal abdominal ganglion (TAG) has a neuronal circuit for a wind-detection system to elicit this behavior. We investigated neuronal transmission from cercal sensory afferent neurons to ascending giant interneurons (GIs). Pharmacological treatment with 500 muM acetylcholine (ACh) increased neuronal activities of ascending interneurons with cell bodies located in the TAG. The effects of ACh antagonists on the activities of identified GIs were examined. The muscarinic ACh antagonist atropine at 3-mM concentration had no obvious effect on the activities of GIs 10-3, 10-2, or 9-3. On the other hand, a 3-mM concentration of the nicotinic ACh antagonist mecamylamine decreased spike firing of these interneurons. Immunohistochemistry using a polyclonal anti-conjugated acetylcholine antibody revealed the distribution of cholinergic neurons in the TAG. The cercal sensory afferent neurons running through the cercal nerve root showed cholinergic immunoreactivity, and the cholinergic immunoreactive region in the neuropil overlapped with the terminal arborizations of the cercal sensory afferent neurons. Cell bodies in the median region of the TAG also showed cholinergic immunoreactivity. This indicates that not only sensory afferent neurons but also other neurons that have cell bodies in the TAG could use ACh as a neurotransmitter.     

Presynaptic inhibition and antidromic discharges in crayfish primary afferents.

The mechanisms of presynaptic inhibition have been studied in sensory afferents of a stretch receptor in an in vitro preparation of the crayfish. Axon terminals of these sensory afferents display primary afferent depolarisations (PADs) mediated by the activation of GABA receptors that open chloride channels. Intracellular labeling of sensory axons by Lucifer yellow combined with GABA immunohistochemistry revealed the presence of close appositions between GABA-immunoreactive boutons and sensory axons close to their first branching point within the ganglion. Electrophysiological studies showed that GABA inputs mediating PADs appear to occur around the first axonal branching point, which corresponds to the area of transition between active and passive propagation of spikes. Moreover, this study demonstrated that whilst shunting appeared to be the sole mechanism involved during small amplitude PADs, sodium channel inactivation occurred with larger amplitude PADs. However, when the largest PADs (>25 mV) are produced, the threshold for spike generation is reached and antidromic action potentials are elicited. The mechanisms involved in the initiation of antidromic discharges were analyzed by combining electrophysiological and simulation studies. Three mechanisms act together to ensure that PAD-mediated spikes are not conveyed distally: 1) the lack of active propagation in distal regions of the sensory axons; 2) the inactivation of the sodium channels around the site where PADs are produced; and 3) a massive shunting through the opening of chloride channels associated with the activation of GABA receptors. The centrally generated spikes are, however, conveyed antidromically in the sensory nerve up to the proprioceptive organ, where they inhibit the activity of the sensory neurons for several hundreds of milliseconds.