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J C Bornstein

Publications and source records attributed to J C Bornstein.

At least 19 recordsLinked to original sources
PubMed2007

Mechanisms underlying nutrient-induced segmentation in isolated guinea pig small intestine.

Mechanisms underlying nutrient-induced segmentation within the gut are not well understood. We have shown that decanoic acid and some amino acids induce neurally dependent segmentation in guinea pig small intestine in vitro. This study examined the neural mechanisms underlying segmentation in the circular muscle and whether the timing of segmentation contractions also depends on slow waves. Decanoic acid (1 mM) was infused into the lumen of guinea pig duodenum and jejunum. Video imaging was used to monitor intestinal diameter as a function of both longitudinal position and time. Circular muscle electrical activity was recorded by using suction electrodes. Recordings from sites of segmenting contractions showed they are always associated with excitatory junction potentials leading to action potentials. Recordings from sites oral and anal to segmenting contractions revealed inhibitory junction potentials that were time locked to those contractions. Slow waves were never observed underlying segmenting contractions. In paralyzed preparations, intracellular recording revealed that slow-wave frequency was highly consistent at 19.5 (SD 1.4) cycles per minute (c/min) in duodenum and 16.6 (SD 1.1) c/min in jejunum. By contrast, the frequencies of segmenting contractions varied widely (duodenum: 3.6-28.8 c/min, median 10.8 c/min; jejunum: 3.0-27.0 c/min, median 7.8 c/min) and sometimes exceeded slow-wave frequencies for that region. Thus nutrient-induced segmentation contractions in guinea pig small intestine do not depend on slow-wave activity. Rather they result from a neural circuit producing rhythmic localized activity in excitatory motor neurons, while simultaneously activating surrounding inhibitory motor neurons.

Action Potentials↗
PubMed2005

Different types of potassium channels underlie the long afterhyperpolarization in guinea-pig sympathetic and enteric neurons.

Ca(2+)-activated K(+) channels play an important role in the control of neuronal excitability via the generation of the afterhyperpolarization. While both small and large conductance Ca(2+)-activated K(+) channels underlie afterhyperpolarizations in different neuron types, the role of intermediate conductance Ca(2+)-activated K(+) channels (IK(Ca)) in the generation of afterhyperpolarizations remains unclear. The effects of blockade of IK(Ca) on guinea pig coeliac and ileal myenteric neurons were studied using single microelectrode current and voltage clamp. In coeliac neurons, TRAM-39, a selective blocker of IK(Ca), depressed the amplitude of the prolonged conductance underlying the slow afterhyperpolarization, (gKCa2) by 57%. In contrast, the conductance underlying the prolonged afterhyperpolarization in AH-type myenteric neurons was unaffected by TRAM-39, although it has been suggested that this AHP is mediated by IK(Ca). In both types of neurons, TRAM-39 did not alter the resting cell properties or the properties of the action potential. TRAM-39 had no effect on the amplitude of the fast component of the afterhyperpolarization present in sympathetic LAH neurons. The results of this study suggest that in sympathetic LAH neurons, activation of IK(Ca) underlies at least part of the prolonged afterhyperpolarization while the nature of the channel underlying the AHP in enteric neurons remains unclear.

Acetonitriles↗
PubMed2005

Slow excitatory post-synaptic potentials in myenteric AH neurons of the guinea-pig ileum are reduced by the 5-hydroxytryptamine7 receptor antagonist SB 269970.

Serotonin (5-HT) is a key modulator of neuronal excitability in the central and peripheral nervous system. In the enteric nervous system, 5-HT causes a slow depolarization in the intrinsic sensory neurons, but the receptor responsible for this has not been correlated with known gene products. The aim of this study was to determine whether the newly characterized 5-HT7 receptor may participate in the 5-HT-mediated depolarization of, and synaptic transmission to, the intrinsic sensory neurons of the guinea-pig ileum. Intracellular electrophysiological recordings were made from intrinsic sensory neurons identified as myenteric AH neurons from guinea-pig ileum. 5-HT (5 microM) applied to the cell body evoked both a fast depolarization (5-HT3 mediated) and/or a slow depolarization (5-HT1P-like). The 5-HT1/5/7 receptor agonist 5-carboxamidotryptamine (5-CT) (5 microM) evoked only a slow depolarization. When the fast depolarization evoked by 5-HT was blocked with granisetron (1 microM, 5-HT3 receptor antagonist), only a slow depolarization remained; this was abolished by the 5-HT7 receptor antagonist SB 269970 (1 microM, control: 14+/-2 mV, granisetron+SB 269970: -1+/-2 mV). The slow depolarization evoked by 5-CT was also significantly reduced by SB 269970 (control: 14+/-1 mV, SB 269970: 5+/-2 mV) suggesting a 5-HT7 receptor was activated by exogenous application of 5-CT and 5-HT. Slow excitatory postsynaptic potentials evoked by stimulating descending neural pathways (containing serotonergic fibers) were reduced by SB 269970 (control: 8+/-3 mV, SB 269970: 3+/-1 mV). However, SB 269970 had no effect on slow excitatory postsynaptic potentials evoked by stimulation of circumferential (tachykinergic) pathways (control: 7+/-1 mV, SB 269970: 6+/-1 mV). These data are consistent with the presence on enteric AH neurons of functional 5-HT7 receptors that participate in slow synaptic transmission.

Animals↗
PubMed2004

Synaptic transmission in simple motility reflex pathways excited by distension in guinea pig distal colon.

We examined specific receptor/transmitter combinations used at functionally identified synapses in ascending and descending reflex pathways of guinea pig distal colon. Excitatory (EJPs) or inhibitory junction potentials (IJPs) were recorded intracellularly from nicardipine-paralyzed circular smooth muscle in either the oral or anal recording chamber of a three-chambered organ bath, respectively. Blockade of synaptic transmission in the central chamber with a 0.25 mM Ca2+/12 mM Mg2+ solution abolished EJPs evoked by distension applied either in the central or the far (anal) chamber. IJPs evoked by distension in the central or the far (oral) chamber were depressed to approximately 50% of control. Hexamethonium (nicotinic receptor antagonist, 200 microM) in the central chamber reduced IJPs evoked by far or central distension to 50%, whereas EJPs evoked by far distension were abolished and EJPs evoked by central distension were reduced to 70% of control. Hexamethonium in the recording chambers reduced both IJPs and EJPs evoked by central distension to approximately 50%. EJPs in the ascending pathway were unaffected by blockade of muscarinic receptors in the central chamber or blockade of neurokinin 3 tachykinin receptors in this or the recording chamber. In the descending pathway, blockade of P2 receptors in the same chambers had only a minor effect on distension-evoked IJPs. Thus some intrinsic sensory neurons of guinea pig colon have long descending projections (>30 mm), but ascending projections of <15 mm. In contrast to the ileum, transmission between ascending or descending interneurons and from sensory neurons to descending interneurons is predominantly via nicotinic receptors; but transmission to inhibitory or excitatory motoneurons and from sensory neurons to ascending interneurons involves nicotinic and other unidentified receptors.

Afferent Pathways↗
PubMed2004

ATP participates in three excitatory postsynaptic potentials in the submucous plexus of the guinea pig ileum.

Synaptic transmission between neurones intrinsic to the wall of the intestine involves multiple neurotransmitters. This study aimed to identify neurotransmitters responsible for non-cholinergic excitatory synaptic transmission in the submucous plexus of the guinea pig ileum. Intracellular recordings were made from secretomotor and vasodilator neurones. A single electrical stimulus to a fibre tract evoked excitatory postsynaptic potentials (EPSPs) with three different time courses - fast, slow and an EPSP with an intermediate time course (latency 96 ms, duration 1.2 s). In all neurones, blocking nicotinic receptors reduced fast EPSPs, but they were abolished in only 57 of 78 neurones. Fast EPSPs were also reduced by P2 purinoceptor blockade (5 of 27 neurones) or 5-HT(3) receptor blockade (3 of 20 neurones). The intermediate EPSP was abolished by P2 receptor blockade (13 of 13 neurones) or by the specific P2Y(1) receptor antagonist MRS 2179 (5 of 5 neurones) and was always preceded by a nicotinic or mixed nicotinic/purinergic fast EPSP. Intermediate EPSPs were observed in over half of all neurones including most non-cholinergic secretomotor neurones identified by immunoreactivity for vasoactive intestinal peptide. The slow EPSP evoked by a single pulse stimulus was also abolished by P2 receptor blockade (5 of 5 neurones) or by MRS 2179 (3 of 3 neurones). We conclude that fast EPSPs in submucous neurones are mediated by acetylcholine acting at nicotinic receptors, ATP acting at P2X receptors and 5-HT acting at 5-HT(3) receptors. Both the intermediate EPSP and the single stimulus slow EPSP are mediated by ATP acting at P2Y(1) receptors.

Acetylcholine↗
PubMed2004

Segmentation induced by intraluminal fatty acid in isolated guinea-pig duodenum and jejunum.

Small intestinal movements depend on the composition of the chyme with mixing predominating at high nutrient levels and propulsion being prevalent at low nutrient levels. The mechanisms coupling nutrients to motility are unknown. We used computer analysis of video recordings of isolated guinea-pig duodenum, jejunum and ileum to examine movements induced by a fatty acid, decanoic acid. Increasing intraluminal pressure past a threshold using control saline consistently evoked propulsive reflexes: lumen-occluding constrictions appeared at the oral end propagating at 20.4 +/- 2.4 mm s(-1) (mean +/-s.d., jejunum) to the anal end before being repeated until the intraluminal pressure was returned to control. Subthreshold pressure increases sometimes evoked a transient series of constrictions appearing at the oral end and propagating anally at 18.4 +/- 4.7 mm s(-1) (jejunum). At basal pressures, decanoic acid dose-dependently induced motor activity consisting of 40-60 s episodes of constrictions separated by 40-200 s periods of quiescence and lasting up to 2 h. Five contraction patterns were identified within episodes including localized stationary constrictions; constrictions that propagated slowly (5-8 mm s(-1)) for short distances orally or anally; and constrictions that propagated orally or anally for the length of the preparation at 14-20 mm s(-1). Decanoic acid induced motor activity was reversibly abolished by tetrodotoxin (3 microm), hyoscine (1 microm) and hexamethonium (100 microm), but was insensitive to blockade of P2 purinoceptors by PPADS (60 microm). Thus, decanoic acid induces motor activity equivalent to segmentation in guinea-pig small intestine in vitro and this depends on intrinsic neural pathways.

Animals↗
PubMed2004

Neurokinin-1 and -3 receptor blockade inhibits slow excitatory synaptic transmission in myenteric neurons and reveals slow inhibitory input.

Recent studies have shown that tachykinins mediate slow synaptic transmission to myenteric AH (afterhyperpolarising) neurons via neurokinin-3 receptors (NK(3)R). This study investigated a similar role for neurokinin-1 receptors (NK(1)R) and compared the effect of selective receptor antagonists on non-cholinergic slow excitatory post-synaptic potentials (EPSPs) recorded in myenteric AH neurons of the guinea-pig ileum. Slow EPSPs evoked by electrical stimulation of circumferentially oriented presynaptic nerves were mimicked by application of senktide, an NK(3)R agonist. [Sar(9),Met(O(2))(11)]-substance P, an NK(1)R agonist, depolarised a smaller number of neurons. SR142801, a selective NK(3)R antagonist (100 nM), inhibited slow EPSPs and responses to senktide, but had no effect on depolarisations evoked by forskolin, an activator of adenylate cyclase. SR140333, a selective NK(1)R antagonist, inhibited slow EPSPs in a subset of neurons and blocked responses to [Sar(9),Met(O(2))(11)]-substance P, but not to senktide or forskolin. Slow EPSPs that were predominantly mediated by NK(1)R had significantly shorter latencies than those due to activation of NK(3)R. After blockade of slow EPSPs, slow hyperpolarizing responses to presynaptic nerve stimulation were revealed in one-third of neurons. These events, which were associated with a decrease in input resistance and blocked by tetrodotoxin, were equated with slow inhibitory postsynaptic potentials. They were abolished by the 5-hydroxytryptamine(1A) receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190), but unaffected by phentolamine, an alpha-adrenoceptor antagonist. In conclusion, these results provide the first direct evidence that NK(1)R mediate some slow excitatory synaptic input to myenteric AH neurons, and suggest that NK(1)R and NK(3)R activate distinct signal transduction pathways. These results also demonstrate that slow inhibitory synaptic transmission, which may be mediated by 5-hydroxytryptamine, is more prevalent in the myenteric plexus than previously indicated.

Adrenergic alpha-Antagonists↗
PubMed2004

Enteric motor and interneuronal circuits controlling motility.

The enteric nervous system regulates intestinal motility. It contains intrinsic sensory neurones, several types of interneurones and excitatory and inhibitory motor neurones. This review summarizes our knowledge of motor neurones and interneurones in simple motility reflex pathways (ascending and descending excitation, descending inhibition) and it focuses on guinea-pig ileum. Excitatory circular muscle motor neurones contain choline acetyltransferase (ChAT) and tachykinins and project orally 0.5-10 mm. They transmit via muscarinic acetylcholine receptors and tachykinins acting at NK1 and NK2 receptors. Inhibitory circular muscle motor neurones contain nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP), project anally up to 25 mm and transmit via ATP, nitric oxide and/or VIP. Ascending interneurones project up to 10 mm orally and contain ChAT and tachykinins. They transmit to each other via ACh at nicotinic receptors (nAChR), but to excitatory motor neurones via both nAChR and NK3 receptors. There are at least three types of descending interneurones and one transmits to inhibitory motor neurones via ATP acting at P2X receptors. NOS-containing descending interneurones receive input via P2Y receptors from other interneurones. Transmission to and from the other descending interneurones (ChAT/5-HT, ChAT/somatostatin) is yet to be characterized.

Animals↗
PubMed2003

Computational model of the migrating motor complex of the small intestine.

The migrating motor complex (MMC) is a cyclic motor pattern with several phases enacted over the entire length of the small intestine. This motor pattern is initiated and coordinated by the enteric nervous system and modulated by extrinsic factors. Because in vitro preparations of the MMC do not exist, it has not been possible to determine the intrinsic nerve circuits that manage this motor pattern. We have used computer simulation to explore the possibility that the controlling circuit is the network of AH/Dogiel type II (AH) neurons. The basis of the model is that recurrent connections between AH neurons cause local circuits to enter a high-firing-rate state that provides the maximal motor drive observed in phase III of the MMC. This also drives adjacent segments of the network causing slow migration. Delayed negative feedback within the circuit, provided by activity-dependent synaptic depression, forces the network to return to rest after passage of phase III. The anal direction of propagation is a result of slight anal bias observed in projections of AH neurons. The model relates properties of neurons to properties of the MMC cycle: phase III migration speed is governed by neuron excitability, MMC cycle length is governed by the rate of recovery of synaptic efficacy, and phase III duration is governed by duration of slow excitatory postsynaptic potentials in AH neurons. In addition, the model makes experimental predictions that can be tested using standard techniques.

Algorithms↗
PubMed2003

Inhibitory cotransmission or after-hyperpolarizing potentials can regulate firing in recurrent networks with excitatory metabotropic transmission.

Recurrent networks of neurons communicating via excitatory connections are common in the nervous system. In the absence of mechanisms to control firing (collectively termed negative feedback), these networks are likely to be bistable and unable to meaningfully encode input signals. In most recurrent circuits, negative feedback is provided by a specialized subpopulation of interneurons, but such neurons are absent from some systems, which therefore require other forms of negative feedback. One such circuit is found within the enteric nervous system of the intestine, where AH/Dogiel type II neurons are interconnected via excitatory synapses acting through metabotropic receptors to produce slow excitatory postsynaptic potentials (slow EPSPs). Negative feedback in this recurrent network may come from either inhibitory postsynaptic potentials arising from the terminals that produce slow EPSPs or from the after hyperpolarizing potentials (AHPs) characteristic of these neurons. We have examined these possibilities using mathematical analysis, based on the Wilson-Cowan model, and computer simulations. Analysis of steady states showed that, under appropriate conditions, both types of negative feedback can provide robust regulation of firing allowing the networks to encode input signals. Numerical simulations were performed using large, anatomically realistic networks with realistic models for metabotropic transmission and suppression of the AHP. In the presence of constant exogenous input, parameters controlling aspects of synaptic events were varied, confirming the analytical results for static stimuli. The simulated networks also responded to time varying inputs in a manner consistent with known physiology. In addition, simulation revealed that neurons in networks with inhibitory contransmission fired in erratic bursts, a phenomenon observed in neurons in unparalysed tissue. Thus, either inhibitory contransmission or AHPs, or both, can allow recurrent networks of AH/Dogiel type II neurons to encode ongoing inputs in a biologically useful way. These neurons appear to be intrinsic primary afferent neurons (IPANs), which implies that the IPANs in a region act in a coordinated fashion.

Action Potentials↗
PubMed2003

Cholinergic transmission to colonic circular muscle of children with slow-transit constipation is unimpaired, but transmission via NK2 receptors is lacking.

Tachykinins (TKs) colocalize with acetylcholine in excitatory motor neurones supplying human colonic circular muscle (CCM). Some children with slow-transit constipation (STC) have reduced TK-immunoreactivity in nerve terminals in CCM suggesting a deficit in neuromuscular transmission. This study aimed to test this possibility. Seromuscular biopsies of transverse colon were obtained laparoscopically from STC children (37, 17 with low density of TK-immunoreactivity). Specimens of transverse (17) and sigmoid colon (20) were obtained from adults undergoing colonic resection for cancer. CCM contractions were measured isotonically and responses to carbachol, neurokinin A (NKA) and electrical field stimulation (EFS) recorded. Carbachol and NKA-evoked contractions in adult and STC colon. Hyoscine (2 micromol L-1) significantly depressed responses to EFS in all preparations. Blockade of NK2 receptors (SR 48968, 2 micromol L-1) significantly depressed EFS-evoked contractions of adult transverse CCM, but had no effect on STC preparations. Thus, neuromuscular transmission in both adults and STC children is predominantly cholinergic and this component is unimpaired in the latter, indicating that reduced TK-immunoreactivity is not a marker for depressed cholinergic responses. Although pharmacologically responsive TK receptors are present in STC colon, we did not detect neuromuscular transmission mediated by release of TKs in these preparations.

Adolescent↗
PubMed2003

Nicotinic transmission at functionally distinct synapses in descending reflex pathways of the rat colon.

We examined descending reflex pathways in the rat colon using intracellular recording techniques. Inhibitory junction potentials (IJPs) were recorded from circular smooth muscle when descending pathways were excited by combined mucosal compression and distension. IJPs were reduced to 71% of control when synaptic transmission was blocked in the oral stimulation chamber of a divided organ bath suggesting that two reflex pathways exist, the one involving descending sensory neurones and the other involving descending interneurones. Hexamethonium (200 micromol L(-1)) in the recording chamber abolished reflexly evoked IJPs, while in the stimulation chamber, it was as effective as synaptic blockade. When hexamethonium was added to a chamber lying between the stimulation and recording chambers, it again sharply depressed IJPs to 27% of control; an extent similar to synaptic blockade. A P2 receptor antagonist did not reveal any purinergic neurotransmission. Either granisetron (5-HT3 receptor antagonist, 1 micromol L(-1)) or SB204070 (5-HT4 receptor antagonist, 1 micromol L(-1)) in the stimulation chamber significantly decreased IJPs; these decreases were not additive. We conclude that some sensory neurones and interneurones in rat colon have long anally projecting axons and that acetylcholine, acting via nicotinic receptors, is the primary neurotransmitter from sensory neurones, to inhibitory motor neurones and between interneurones.

Action Potentials↗
PubMed2002

Slow excitatory synaptic potentials evoked by distension in myenteric descending interneurones of guinea-pig ileum.

The functional significance of the slow excitatory synaptic potentials (EPSPs) in myenteric neurones is unknown. We investigated this using intracellular recording from myenteric neurones in guinea-pig ileum, in vitro. In all, 121 neurones responded with fast EPSPs to distension of the intestine oral to the recording site. In 28 of these neurones, distension also evoked depolarizations similar to the slow EPSPs evoked by electrical stimulation in the same neurones. Intracellular injection of biocytin and immunohistochemistry revealed that neurones responding to distension with slow EPSPs were descending interneurones, which were immunoreactive for nitric oxide synthase (NOS). Other neurones, including inhibitory motor neurones and interneurones lacking NOS, did not respond to distension with slow EPSPs, but many had slow EPSPs evoked electrically. Slow EPSPs evoked electrically or by distension in NOS-immunoreactive descending interneurones were resistant to blockade of NK(1) or NK(3) tachykinin receptors (SR 140333, 100 nM; SR 142801, 100 nM, respectively) and group I metabotropic glutamate receptors (PHCCC, 10-30 microM), when the antagonists were applied in the recording chamber of a two-chambered organ bath. However, slow EPSPs evoked electrically in inhibitory motor neurones were substantially depressed by SR 140333 (100 nM). Blockade of synaptic transmission in the stimulation chamber of the organ bath abolished slow EPSPs evoked by distension, indicating that they arose from activity in interneurones, and not from anally directed, intrinsic sensory neurones. Thus, distension evokes slow EPSPs in a subset of myenteric neurones, which may be important for intestinal motility.

Animals↗
PubMed2002

ATP and 5-HT are the principal neurotransmitters in the descending excitatory reflex pathway of the guinea-pig ileum.

Neurotransmission underlying descending excitatory reflexes evoked by distension was studied in opened segments of guinea-pig ileum and compared with peristalsis in intact segments. The opened segments were distended by inflating a balloon against the serosa at the oral end and changes in muscle length recorded from the anal end. Distension elicited contractions in both circular (CM) and longitudinal (LM) muscle layers. Granisetron, a 5-HT(3) receptor antagonist (10 nmol L-1 to 1 micromol L-1) reduced CM contractions (24% control), without affecting the LM. The P2 receptor antagonist, pyridoxal phosphate-6-azopheyl-2',4'-disulphonic acid (PPADS; 10 micromol L-1), reduced CM contractions to 31% and LM contractions to 39%. Hexamethonium (500 micromol L-1) enhanced LM contractions, but had no effect on CM contractions. Granisetron (1 micromol L-1) had no significant effect on the threshold for peristaltic contractions in a modified Trendelenburg preparation, but decreased the decay time of these contractions by 37%. PPADS (10 micromol L-1) had no significant effect in this preparation. Thus, the descending excitatory pathways to CM and LM can be distinguished pharmacologically; the former depend on 5-HT(3) and P2 ATP receptors, the latter are independent of 5-HT(3) receptors. Nicotinic receptors may have little part in either pathway. These properties differ from conventional peristaltic reflexes, which are effectively abolished by nicotinic blockade.

Adenosine Triphosphate↗
PubMed2000

Descending inhibitory reflexes involve P2X receptor-mediated transmission from interneurons to motor neurons in guinea-pig ileum.

The role of P2X receptors in descending inhibitory reflexes evoked by distension or mucosal distortion in the guinea-pig ileum was studied using intracellular recording from the circular muscle in a two-chambered organ bath. This allowed separate superfusion of the sites of reflex stimulation and recording, thereby allowing drugs to be selectively applied to different parts of the reflex pathway. Inhibitory junction potentials (IJPs) evoked by electrical field stimulation (EFS) in the recording chamber were compared with those evoked during reflexes to control for effects of P2 receptor antagonists on neuromuscular transmission. The P2 receptor antagonists suramin (100 microM) and pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (10 and 60 microM; PPADS), when added to the recording chamber, depressed reflexly evoked IJPs significantly more than those evoked by EFS. In particular, 10 microM PPADS depressed IJPs evoked by distension or mucosal distortion by about 50 %, but had little effect on IJPs evoked by EFS. Blockade of synaptic transmission in the stimulation chamber with a low Ca2+-high Mg2+ solution depressed, but did not abolish, IJPs evoked by distension. The residual reflex IJPs were unaffected by PPADS (10 microM), hyoscine (1 microM), hyoscine plus hexamethonium (200 microM), or hysocine plus hexamethonium plus PPADS in the recording chamber. We conclude that P2X receptors are important for synaptic transmission from descending interneurons to inhibitory motor neurons in descending inhibitory reflex pathways of guinea-pig ileum. Transmission from anally directed axons of distension-sensitive intrinsic sensory neurons to inhibitory motor neurons is unlikely to involve P2X, muscarinic or nicotinic receptors.

Animals↗
PubMed2000

A computer simulation of recurrent, excitatory networks of sensory neurons of the gut in guinea-pig.

Intrinsic sensory neurons of the intestine are connected together to form a recurrent network. They interact by slow excitatory post synaptic potentials (EPSPs), which have a complex dependence on the pattern of input. These networks are unstable and unable to give graded responses to sensory input without some form of inhibition, but inhibitory synaptic potentials are rare in this system. Intrinsic sensory neurons have a characteristic after-hyperpolarization (AHP), but this is depressed during slow EPSPs. To test whether AHPs can provide the inhibition necessary for stability, AHPs, slow EPSPs and their interactions were included in a computer simulation of realistic sensory neuron networks. Residual AHPs as small as 1% of control were found to lead to stable networks capable of giving graded responses.

Action Potentials↗