An identified cerebral interneuron initiates different elements of prey capture behavior in the pteropod mollusc,Clione limacina

The prey capture phase of feeding behavior in the pteropod molluscClione limacina consists of an explosive extrusion of buccal cones, specialized oral appendages which are used to catch the prey, and significant acceleration of swimming. Several groups of neurons which control different components of prey capture behavior inClione have been previously identified in the CNS. However, the question of their coordination in order to develop a normal behavioral reaction still remains open. We describe here a cerebral interneuron which has wide-spread excitatory and inhibitory effects on a number of neurons in the cerebral and pedal ganglia, directed toward the initiation of prey capture behavior inClione. This bilaterally symmetrical neuron, designated Cr-PC (Cerebral interneuron initiating Prey Capture), produced monosynaptic activation of Cr-A motoneurons, which control buccal cone extrusion, and inhibition of Cr-B and Cr-L motoneurons, whose spike activities maintain buccal cones in a withdrawn position inside the head in non-feeding animals. In addition, Cr-PC produced monosynaptic activation of a number of swim motoneurons and interneurons of the swim central pattern generator (CPG) in the pedal ganglia, pedal serotonergic Pd-SW neurons involved in a peripheral modulation of swimming and the serotonergic Heart Excitor neuron.     

Prey capture phase of feeding behavior in the pteropod mollusc,clione limacina: neuronal mechanisms

The prey capture phase of feeding behavior in the pteropod mollusc Clione limacina consists of an explosive extrusion of buccal cones, specialized structures which are used to catch the prey, and acceleration of swimming with frequent turning and looping produced by tail bend. A system of neurons which control different components of prey capture behavior in Clione has been identified in the cerebral ganglia. Cerebral B and L neurons produce retraction of buccal cones and tightening of the lips over them — their spontaneous spike activities maintain buccal cones in the withdrawn position. Cerebral A neurons inhibit B and L cells and produce opening of the lips and extrusion of buccal cones. A pair of cerebral interneurons C-BM activates cerebral A neurons and synchronously initiates the feeding motor program in the buccal ganglia. Cerebral T neurons initiate acceleration of swimming and produce tail bending which underlies turning and looping during the prey capture. Both tactile and chemical inputs from the prey produce activation of cerebral A and T neurons. This reaction appears to be specific, since objects other than alive Limacina or Limacina juice do not initiate activities of A and T neurons.     

Modulation of swimming speed in the pteropod mollusc,Clione limacina: Role of a compartmental serotonergic system

In locomotory systems, the central pattern generator and motoneuron output must be modulated in order to achieve variability in locomotory speed, particularly when speed changes are important components of different behavior acts. The swimming system of the pteropod molluscClione limacina is an excellent model system for investigating such modulation. In particular, a system of central serotonergic neurons has been shown to be intimately involved in regulating output of the locomotory pattern generator and motor system ofClione. There are approximately 27 pairs of serotonin-immunoreactive neurons in the central nervous system ofClione, with about 75% of these identified. The majority of these identified immunoreactive neurons are involved in various aspects of locomotory speed modulation. A symmetrical cluster of pedal serotonergic neurons serves to increase wing contractility without affecting wing-beat frequency or motoneuron activity. Two clusters of cerebral cells produce widespread responses that lead to an increase in pattern generator cycle frequency, recruitment of swim motoneurons, activation of the pedal serotonergic neurons and excitation of the heart excitor neuron. A pair of ventral cerebral neurons provides weak excitatory inputs to the swimming system, and strongly inhibits neurons of the competing whole-body withdrawal network. Overall, the serotonergic system inClione is compartmentalized so that each subsystem (usually neuron cluster) can act independently or in concert to produce variability in locomotory speed.     

Radular mechanosensory neuron in the buccal ganglia of the terrestrial slug,Incilaria fruhstorferi

A radular mechanosensory neuron, RM, was identified in the buccal ganglia of Incilaria fruhstorferi. Fine neurites ramified bilaterally in the buccal ganglia, and main neurites entered the subradular epithelium via buccal nerve 3 (n3). When the radula was distorted by bending, RM produced an afferent spike which was preceded by an axonic spike recorded at n3. The response of RM to radular distortion was observed even in the absence of Ca²⁺, which drastically suppressed chemical synaptic interactions. Therefore, RM was concluded to be a primary radular mechanoreceptor.During rhythmic buccal motor activity induced by food or electrical stimulation of the cerebrobuccal connective, RM received excitatory input during the radular retraction phase. In the isolated buccal ganglia connected to the radula via n3s, the afferent spike, which had been evoked by electrical stimulation of the subradular epithelium, was broadened with the phasic excitatory input. Since the afferent spike was also broadened by current injection into the soma, depolarization due to the phasic input may have produced the spike broadening.Spike broadening was also observed during repetitive firing evoked by current injection. The amplitude of the excitatory postsynaptic potential in a follower neuron increased depending on the spike broadening of RM.Abbreviations CBC cerebrobuccal connective - EPSP excitatory postsynaptic potential - n1,n3 buccal nerves 1 and 3 - RBMA rhythmic buccal motor activity - RM radular mechanosensory neuron - SMT supramedian radular tensor neuron     

Neural mechanism generating firing patterns in jaw motoneurons during the food-induced response in Aplysia kurodai

1. In each right and left buccal ganglia of Aplysia kurodai, we identified 4 premotor neurons impinging on the ipsilateral jaw-closing and -opening motoneurons. Three of them (MA1 neurons) had features of multifunctional neurons. Current-induced spikes in the MA1 neurons produced excitatory junction potentials (EJPs) in the buccal muscle fibers. In addition, tactile stimulation of the buccal muscle surface produced a train of spikes in the MA1 neurons without synaptic input. The other neuron (MA2) had only a premotor function. 2. The MA1 and MA2 neurons had similar synaptic effects on the jaw-closing and -opening motoneurons. Current-induced spikes in the premotor neurons gave rise to monosynaptic inhibitory postsynaptic potentials (IPSPs) in the ipsilateral jaw-closing motoneurons. Simultaneously, spikes in one of the MA1 neurons and the MA2 also gave rise to monosynaptic excitatory postsynaptic potentials (EPSPs) in the ipsilateral jaw-opening motoneuron. 3. The IPSPs and the EPSPs induced by spikes in the premotor neurons were reversibly blocked by d-tubocurarine and hexamethonium, respectively, suggesting that the MA1 and MA2 neurons are cholinergic. 4. When depolarizing and hyperpolarizing current pulses were passed into one premotor neuron, attenuated but similar potential changes were produced in another randomly selected premotor neuron in the same ganglion, suggesting that they are electronically coupled.     

Modelling Feedback Excitation,Pacemaker Properties and Sensory Switching of Electrically Coupled Brainstem Neurons Controlling Rhythmic Activity

What cellular and network properties allow reliable neuronal rhythm generation or firing that can be started and stopped by brief synaptic inputs? We investigate rhythmic activity in an electrically-coupled population of brainstem neurons driving swimming locomotion in young frog tadpoles, and how activity is switched on and off by brief sensory stimulation. We build a computational model of 30 electrically-coupled conditional pacemaker neurons on one side of the tadpole hindbrain and spinal cord. Based on experimental estimates for neuron properties, population sizes, synapse strengths and connections, we show that: long-lasting, mutual, glutamatergic excitation between the neurons allows the network to sustain rhythmic pacemaker firing at swimming frequencies following brief synaptic excitation; activity persists but rhythm breaks down without electrical coupling; NMDA voltage-dependency doubles the range of synaptic feedback strengths generating sustained rhythm. The network can be switched on and off at short latency by brief synaptic excitation and inhibition. We demonstrate that a population of generic Hodgkin-Huxley type neurons coupled by glutamatergic excitatory feedback can generate sustained asynchronous firing switched on and off synaptically. We conclude that networks of neurons with NMDAR mediated feedback excitation can generate self-sustained activity following brief synaptic excitation. The frequency of activity is limited by the kinetics of the neuron membrane channels and can be stopped by brief inhibitory input. Network activity can be rhythmic at lower frequencies if the neurons are electrically coupled. Our key finding is that excitatory synaptic feedback within a population of neurons can produce switchable, stable, sustained firing without synaptic inhibition.     

A comparison of human motoneuron data to simulated data using cat motoneuron models.

The response of repetitively firing human motoneurons to a composite excitatory input was evaluated. It was clearly shown that the response of the motoneurons to the transient input decreased with an increase in the background firing rate of the cell. The current model of repetitively firing human motoneurons could not account for this experimental result. Therefore, a compartmental modelling approach was used to simulate the repetitive firing properties of anaesthetised cat motoneurons under current clamp conditions. The modelled motoneurons were used in simulations similar to the experimental paradigms where the response to a composite excitatory input was evaluated at different background firing rates. The motoneuron models also showed a decrease in response to the excitatory input at faster background firing rates. The results suggest that human motoneurons are more comparable to motoneurons in the anaesthetised cat preparation than formerly thought. The results also demonstrate that the apparent efficacy of a synaptic input may be modulated by changes in background firing rate of the postsynaptic neuron.     

Peptidergic motoneurons in the buccal ganglia of Aplysia californica Immunocytochemical,morphological, and physiological characterizations

Summary We used physiological recordings, intracellular dye injections and immunocytochemistry to further identify and characterize neurons in the buccal ganglia of Aplysia calif ornica expressing Small Cardioactive Peptide-like immunoreactivity (SCP-LI). Neurons were identified based upon soma size and position, input from premotor cells B4 and B5, axonal projections, muscle innervation patterns, and neuromuscular synaptic properties. SCP-LI was observed in several large ventral neurons including B6, B7, B9, B10, and B11, groups of s1 and s2 cluster cells, at least one cell located at a branch point of buccal nerve n2, and the previously characterized neurons B1, B2 and B15.B6, B7, B9, B10 and B11 are motoneurons to intrinsic muscles of the buccal mass, each displaying a unique innervation pattern and neuromuscular plasticity. Combined, these motoneurons innervate all major intrinsic buccal muscles (I1/I3, I2, I4, I5, I6). Correspondingly, SCP-LI processes were observed on all of these muscles. Innervation of multiple nonhomologous buccal muscles by individual motoneurons having extremely plastic neuromuscular synapses, represents a unique form of neuromuscular organization which is prevalent in this system. Our results show numerous SCPergic buccal motoneurons with widespread ganglionic processes and buccal muscle innervation, and support extensive use of SCPs in the control of feeding musculature.Abbreviations SCP-LI small cardioactive peptide-like immunoreactivity - PSC postsynaptic current - EPSP excitatory postsynaptic potential - IPSP inhibitory postsynaptic potential - FI facilitation index - TMR time to maximal response     

Models for unambiguousE-vector navigation in the bee

Summary The metacerebral giant (MCG) neurons of the molluskPleurobranchaea have been analyzed using a wide range of methods (cobalt staining, histochemical, biophysical and electrophysiological) on several types of preparations (isolated nervous systems, semi-intact preparations, and behaving whole-animal preparations). The MCG is serotonergic. The bilaterally-symmetrical neurons have somata in the anterior brain. Each MCG neuron sends an axon out the ipsilateral mouth nerve of the brain and also into the ipsilateral cerebrobuccal connective which descends to the buccal ganglion. The descending axon sends one or more branches out most buccal nerves.The MCG makes mono- and polysynaptic chemical excitatory and inhibitory connections with identified feeding motoneurons in the buccal ganglion. In quiescent preparations (isolated CNS or semi-intact), MCG stimulation caused coordinated eversion activity followed immediately by withdrawal activity. During an ongoing feeding rhythm (spontaneous output or induced by stimulation of the stomatogastric nerve), tonic stimulation of one or both MCG's at physiological discharge frequencies typically caused a significant increase in the frequency of the rhythm, and usually emphasized the eversion component at the expense of the withdrawal component. Phasic stimulation of one or both MCG's at physiological discharge frequencies and in normal discharge patterns (bursts; see below) accelerated and phaselocked the feeding rhythm.The MCG neurons receive synaptic feedback from identified neurons in the feeding network. Brain motoneurons are reciprocally coupled with the MCG by non-rectifying electrical synapses, while buccal ganglion neurons (the previously identified corollary discharge neurons) inhibit the MCG. Recordings from the MCG during cyclic feeding show that it discharges cyclically and that its membrane potential oscillates in phase with the feeding rhythm, presumably reflecting the above synaptic feedback. Two biophysical properties of the MCG membrane, namely anomalous rectification and postspike conductance increase, are presumed to contribute to the MCG's oscillatory activity.Chemosensory (food stimuli) and mechanosensory inputs from the oral veil excite the MCG's. In whole-animal preparations, these sensory inputs typically cause discharge in the MCG's and other descending neurons, accompanied by feeding motor output.The data collectively suggest that the MCG's ofPleurobranchaea are members of a population of neurons that normally function to command (i.e., arouse, initiate and sustain) the rhythmic feeding behavior. The demonstrated central feedback to the MCG is presumed to amplify these command functions.Supported by an NIH Postdoctoral Fellowship (1 F22 NS00511) to R.G. and NIH Research Grants NS 09050 and MH 23254 to W.J.D. We thank Kathryn H. Britton for histological assistance. We also thank Mark P. Kovac, who produced the records of Figures 8 and 18, for permission to reproduce them here.     

Activity-dependent induction of facilitation,depression, and post-tetanic potentiation at an insect central synapse

Summary In Manduca sexta larvae, sensory neurons innervating planta hairs on the tips of the prolegs make monosynaptic excitatory connections with motoneurons innervating proleg retractor muscles. Tactile stimulation of the hairs evokes reflex retraction of the proleg. In this study we examined activity-dependent changes in the amplitude of the excitatory postsynaptic potentials (EPSPs) evoked in a proleg motoneuron by stimulation of individual planta hair sensory neurons. Deflection of a planta hair caused a phasic-tonic response in the sensory neuron, with a mean peak instantaneous firing frequency of >300 Hz, and a tonic firing rate of 10–20 Hz. Direct electrical stimulation was used to activate individual sensory neurons to fire at a range of frequencies including those observed during natural stimulation of the hair. At relatively low firing rates (e.g., 1 Hz), EPSP amplitude was stable indefinitely. At higher instantaneous firing frequencies (>10 Hz), EPSPs were initially facilitated, but continuous stimulation led rapidly to synaptic depression. High-frequency activation of a sensory neuron could also produce post-tetanic potentiation, in which EPSP amplitude remained elevated for several min following a stimulus train. Facilitation, depression, and post-tetanic potentiation all appeared to be presynaptic phenomena. These activity-dependent changes in sensory transmission may contribute to the behavioral plasticity of the proleg withdrawal reflex observed in intact insects.Abbreviations ACh acetylcholine - AChE acetylcholine esterase - CNS central nervous system - EPSP excitatory postsynaptic potential - I _h injected hyperpolarizing current - LTP long-term potentiation - PPR principal planta retractor motoneuron - PTP post-tetanic potentiation - R _in input resistance - V _h hyperpolarized potential - V _m membrane potential - VN ventral nerve - VNA anterior branch of the ventral nerve - V _r resting potential.     

Emergence of network structure due to spike-timing-dependent plasticity in recurrent neuronal networks. II. Input selectivity—symmetry breaking

Spike-timing-dependent plasticity (STDP) is believed to structure neuronal networks by slowly changing the strengths (or weights) of the synaptic connections between neurons depending upon their spiking activity, which in turn modifies the neuronal firing dynamics. In this paper, we investigate the change in synaptic weights induced by STDP in a recurrently connected network in which the input weights are plastic but the recurrent weights are fixed. The inputs are divided into two pools with identical constant firing rates and equal within-pool spike-time correlations, but with no between-pool correlations. Our analysis uses the Poisson neuron model in order to predict the evolution of the input synaptic weights and focuses on the asymptotic weight distribution that emerges due to STDP. The learning dynamics induces a symmetry breaking for the individual neurons, namely for sufficiently strong within-pool spike-time correlation each neuron specializes to one of the input pools. We show that the presence of fixed excitatory recurrent connections between neurons induces a group symmetry-breaking effect, in which neurons tend to specialize to the same input pool. Consequently STDP generates a functional structure on the input connections of the network.     

Synchronization and sensitivity enhancement of the Hodgkin-Huxley neurons due to inhibitory inputs

Recent experimental results imply that inhibitory postsynaptic potentials can play a functional role in realizing synchronization of neuronal firing in the brain. In order to examine the relation between inhibition and synchronous firing of neurons theoretically, we analyze possible effects of synchronization and sensitivity enhancement caused by inhibitory inputs to neurons with a biologically realistic model of the Hodgkin-Huxley equations. The result shows that, after an inhibitory spike, the firing probability of a single postsynaptic neuron exposed to random excitatory background activity oscillates with time. The oscillation of the firing probability can be related to synchronous firing of neurons receiving an inhibitory spike simultaneously. Further, we show that when an inhibitory spike input precedes an excitatory spike input, the presence of such preceding inhibition raises the firing probability peak of the neuron after the excitatory input. The result indicates that an inhibitory spike input can enhance the sensitivity of the postsynaptic neuron to the following excitatory spike input. Two neural network models based on these effects on postsynaptic neurons caused by inhibitory inputs are proposed to demonstrate possible mechanisms of detecting particular spatiotemporal spike patterns. Received: 15 April 1999 /Accepted in revised form: 25 November 1999     

Modulation of the feeding system by a radular mechanosensory neuron in the terrestrial slug,Incilaria fruhstorferi

We investigated the modulatory role of a radular mechanoreceptor (RM) in the feeding system of Incilaria. RM spiking induced by current injection evoked several cycles of rhythmic buccal motor activity in quiescent preparations, and this effect was also observed in preparations lacking the cerebral ganglia. The evoked rhythmic activity included sequential activation of the inframedian radular tensor, the supramedian radular tensor, and the buccal sphincter muscles in that order.In addition to the generation of rhythmic motor activity, RM spiking enhanced tonic activities in buccal nerve 1 as well as in the cerebrobuccal connective, showing a wide excitatory effect on buccal neurons. The excitatory effect was further examined in the supramedian radular tensor motoneuron. RM spiking evoked biphasic depolarization in the tensor motoneuron consisting of fast excitatory postsynaptic potentials and prolonged depolarization lasting after termination of RM spiking. These depolarizations also occurred in high divalent cation saline, suggesting that they were both monosynaptic.When RM spiking was evoked in the fictive rasp phase during food-induced buccal motor rhythm, the activity of the supramedian radular tensor muscle showed the greatest enhancement of the three muscles tested, while the rate of ongoing rhythmic motor activity showed no increase.Abbreviations CPG central pattern generator - EPSP excitatory postsynaptic potential - RBMA rhythmic buccal motor activity - RM radular mechanosensory neuron - SMT supramedian radular tensor neuron     

Longitudinal neuronal organization and coordination in a simple vertebrate: a continuous,semi-quantitative computer model of the central pattern generator for swimming in young frog tadpoles

When frog tadpoles hatch their swimming requires co-ordinated contractions of trunk muscles, driven by motoneurons and controlled by a Central Pattern Generator (CPG). To study this co-ordination we used a 3.5 mm long population model of the young tadpole CPG with continuous distributions of neurons and axon lengths as estimated anatomically. We found that: (1) alternating swimming-type activity fails to self-sustain unless some excitatory interneurons have ascending axons, (2) a rostro-caudal (R-C) gradient in the distribution of excitatory premotor interneurons with short axons is required to obtain the R-C gradient in excitation and resulting progression of motoneuron firing necessary for forward swimming, (3) R-C delays in motoneuron firing decrease if excitatory motoneuron to premotor interneuron synapses are present, (4) these feedback connections and the electrical synapses between motoneurons synchronise motoneuron discharges locally, (5) the above findings are independent of the detailed membrane properties of neurons.     

Physiological characteristics and reflex activation of DUM (octopaminergic) neurons of locust metathoracic ganglion

Intracellular recordings were made from single or pairs of somata of the dorsal unpaired median (DUM) neurons of the metathoracic ganglion of the locust Schistocerca gregaria and the grasshopper Romalea microptera, during reflex actions, direct electric excitation and orthodromic and antidromic neural stimulation. Some, possibly all, of these neurons are unique, identifiable individuals in regard to their targets, which are specific peripheral muscles. Their physiological properties and the ways they are activated synaptically are, however, similar. Large, overshooting action potentials, comprising three components, occur. The first component in time is small and represents an excitatory synaptic potential for orthodromic stimulation or an axon spike (AS) for antidromic stimulation, electrotonically conducted into the soma. The second component is larger, being an electrotonically conducted integrating segment spike (ISS). The final component is the soma spike (SS). Neither AS nor ISS have a late positive phase, but there is a large, prolonged one for SS. The latter, combined with rapid accommodation, determine a low maximum firing rate for the neurons. Most nerves entering the ganglion make excitatory inputs onto each DUM neuron, which is readily driven to spike by electric excitation of either connective. There is a great deal of spontaneous excitatory synaptic input to each DUM neuron and a high proportion of it is common. Although there is no detectable electrical coupling between the cells, there is about 30% synchronous firing, apparently due to the common inputs; independent excitation and inhibition also occur. All sensory modalities tested have inputs to the neurons, which tend to fire constantly at a low rate (1 per 3–4 sec). In reflex actions, DUM neurons tend to fire before motor output occurs. It is suggested that the cells will be found to have many functions serving a general role comparable to that achieved by the release of adrenaline in vertebrates.     

Local interneurons and information processing in the olfactory glomeruli of the moth Manduca sexta

Intracellular recordings were made from the major neurites of local interneurons in the moth antennal lobe. Antennal nerve stimulation evoked 3 patterns of postsynaptic activity: (i) a short-latency compound excitatory postsynaptic potential that, based on electrical stimulation of the antennal nerve and stimulation of the antenna with odors, represents a monosynaptic input from olfactory afferent axons (71 out of 86 neurons), (ii) a delayed activation of firing in response to both electrical- and odor-driven input (11 neurons), and (iii) a delayed membrane hyperpolarization in response to antennal nerve input (4 neurons).Simultaneous intracellular recordings from a local interneuron with short-latency responses and a projection (output) neuron revealed unidirectional synaptic interactions between these two cell types. In 20% of the 30 pairs studied, spontaneous and current-induced spiking activity in a local interneuron correlated with hyperpolarization and suppression of firing in a projection neuron. No evidence for recurrent or feedback inhibition of projection neurons was found. Furthermore, suppression of firing in an inhibitory local interneuron led to an increase in firing in the normally quiescent projection neuron, suggesting that a disinhibitory pathway may mediate excitation in projection neurons. This is the first direct evidence of an inhibitory role for local interneurons in olfactory information processing in insects. Through different types of multisynaptic interactions with projection neurons, local interneurons help to generate and shape the output from olfactory glomeruli in the antennal lobe.Abbreviations AL antennal lobe - EPSP excitatory postsynaptic potential - GABA -aminobutyric acid - IPSP inhibitory postsynaptic potential - LN local interneuron - MGC macroglomerular complex - OB olfactory bulb - PN projection neuron - TES N-tris[hydroxymethyl]methyl-2-aminoethane-sulfonic acid     

Recurrent networks of submucous neurons controlling intestinal secretion: a modeling study

Secretomotor neurons, immunoreactive for vasoactive intestinal peptide (VIP), are important in controlling chloride secretion in the small intestine. These neurons form functional synapses with other submucosal VIP neurons and transmit via slow excitatory postsynaptic potentials (EPSPs). Thus they form a recurrent network with positive feedback. Intrinsic sensory neurons within the submucosa are also likely to form recurrent networks with positive feedback, provide substantial output to VIP neurons, and receive input from VIP neurons. If positive feedback within recurrent networks is sufficiently large, then neurons in the network respond to even small stimuli by firing at their maximum possible rate, even after the stimulus is removed. However, it is not clear whether such a mechanism operates within the recurrent networks of submucous neurons. We investigated this question by performing computer simulations of realistic models of VIP and intrinsic sensory neuron networks. In the expected range of electrophysiological properties, we found that activity in the VIP neuron network decayed slowly after cessation of a stimulus, indicating that positive feedback is not strong enough to support the uncontrolled firing state. The addition of intrinsic sensory neurons produced a low stable firing rate consistent with the common finding that basal secretory activity is, in part, neurogenic. Changing electrophysiological properties enables these recurrent networks to support the uncontrolled firing state, which may have implications with hypersecretion in the presence of enterotoxins such as cholera-toxin.     

A multivariate population density model of the dLGN/PGN relay

Using a population density approach we study the dynamics of two interacting collections of integrate-and-fire-or-burst (IFB) neurons representing thalamocortical (TC) cells from the dorsal lateral geniculate nucleus (dLGN) and thalamic reticular (RE) cells from the perigeniculate nucleus (PGN). Each population of neurons is described by a multivariate probability density function that satisfies a conservation equation with appropriately defined probability fluxes and boundary conditions. The state variables of each neuron are the membrane potential and the inactivation gating variable of the low-threshold Ca²⁺ current I_T. The synaptic coupling of the populations and external excitatory drive are modeled by instantaneous jumps in the membrane potential of postsynaptic neurons. The population density model is validated by comparing its response to time-varying retinal input to Monte Carlo simulations of the corresponding IFB network composed of 100 to 1000 cells per population. In the absence of retinal input, the population density model exhibits rhythmic bursting similar to the 7 to 14 Hz oscillations associated with slow wave sleep that require feedback inhibition from RE to TC cells. When the TC and RE cell potassium leakage conductances are adjusted to represent cholingergic neuromodulation and arousal of the network, rhythmic bursting of the probability density model may either persists or be eliminated depending on the number of excitatory (TC to RE) or inhibitory (RE to TC) connections made by each presynaptic cell. When the probability density model is stimulated with constant retinal input (10–100 spikes/sec), a wide range of responses are observed depending on cellular parameters and network connectivity. These include asynchronous burst and tonic spikes, sleep spindle-like rhythmic bursting, and oscillations in population firing rate that are distinguishable from sleep spindles due to their amplitude, frequency, or the presence of tonic spikes. In this context of dLGN/PGN network modeling, we find the population density approach using 2,500 mesh points and resolving membrane voltage to 0.7 mV is over 30 times more efficient than 1000-cell Monte Carlo simulations. Action Editor: David Golomb     

Acetylcholine elongates neuronal growth cone filopodia via activation of nicotinic acetylcholine receptors

In addition to acting as a classical neurotransmitter in synaptic transmission, acetylcholine (ACh) has been shown to play a role in axonal growth and growth cone guidance. What is not well understood is how ACh acts on growth cones to affect growth cone filopodia, structures known to be important for neuronal pathfinding. We addressed this question using an identified neuron (B5) from the buccal ganglion of the pond snail Helisoma trivolvis in cell culture. ACh treatment caused pronounced filopodial elongation within minutes, an effect that required calcium influx and resulted in the elevation of the intracellular calcium concentration ([Ca]_i). Whole‐cell patch clamp recordings showed that ACh caused a reduction in input resistance, a depolarization of the membrane potential, and an increase in firing frequency in B5 neurons. These effects were mediated via the activation of nicotinic acetylcholine receptors (nAChRs), as the nAChR agonist dimethylphenylpiperazinium (DMPP) mimicked the effects of ACh on filopodial elongation, [Ca]_i elevation, and changes in electrical activity. Moreover, the nAChR antagonist tubucurarine blocked all DMPP‐induced effects. Lastly, ACh acted locally at the growth cone, because growth cones that were physically isolated from their parent neuron responded to ACh by filopodial elongation with a similar time course as growth cones that remained connected to their parent neuron. Our data revealed a critical role for ACh as a modulator of growth cone filopodial dynamics. ACh signaling was mediated via nAChRs and resulted in Ca influx, which, in turn, caused filopodial elongation. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 487–501, 2013