Slow Synaptic Potentials Research Articles

Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging.

Calcium imaging is a versatile experimental approach capable of resolving single neurons with single-cell spatial resolution in the brain. Electrophysiological recordings provide high temporal, but limited spatial resolution, because of the geometrical inaccessibility of the brain. An approach that integrates the advantages of both techniques could provide new insights into functions of neural circuits. Here, we report a transparent, flexible neural electrode technology based on graphene, which enables simultaneous optical imaging and electrophysiological recording. We demonstrate that hippocampal slices can be imaged through transparent graphene electrodes by both confocal and two-photon microscopy without causing any light-induced artefacts in the electrical recordings. Graphene electrodes record high-frequency bursting activity and slow synaptic potentials that are hard to resolve by multicellular calcium imaging. This transparent electrode technology may pave the way for high spatio-temporal resolution electro-optic mapping of the dynamic neuronal activity.

Efferent Fibers Innervate Gustatory and Mechanosensitive Afferent Fibers in Frog Fungiform Papillae

A possibility of efferent innervation of gustatory and mechanosensitive afferent fiber endings was studied in frog fungiform papillae with a suction electrode. The amplitude of antidromic impulses in a papillary afferent fiber induced by antidromically stimulating an afferent fiber of glossopharyngeal nerve (GPN) with low voltage pulses was inhibited for 40 s after the parasympathetic efferent fibers of GPN were stimulated orthodromically with high voltage pulses at 30 Hz for 10 s. This implies that electrical positivity of the outer surface of papillary afferent membrane was reduced by the efferent fiber-induced excitatory postsynaptic potential. The inhibition of afferent responses in the papillae was blocked by substance P receptor blocker, L-703,606, indicating that substance P is probably released from the efferent fiber terminals. Slow negative synaptic potential, which corresponded to a slow depolarizing synaptic potential, was extracellularly induced in papillary afferent terminals for 45 s by stimulating the parasympathetic efferent fibers of GPN with high voltage pulses at 30 Hz for 10 s. This synaptic potential was also blocked by L-703,606. These data indicate that papillary afferent fiber endings are innervated by parasympathetic efferent fibers.

Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease

G protein-gated inwardly rectifying potassium (GIRK) channels hyperpolarize neurons in response to activation of many different G protein-coupled receptors and thus control the excitability of neurons through GIRK-mediated self-inhibition, slow synaptic potentials and volume transmission. GIRK channel function and trafficking are highly dependent on the channel subunit composition. Pharmacological investigations of GIRK channels and studies in animal models suggest that GIRK activity has an important role in physiological responses, including pain perception and memory modulation. Moreover, abnormal GIRK function has been implicated in altering neuronal excitability and cell death, which may be important in the pathophysiology of diseases such as epilepsy, Down's syndrome, Parkinson's disease and drug addiction. GIRK channels may therefore prove to be a valuable new therapeutic target.

Nitric oxide enhances inhibitory synaptic transmission and neuronal excitability in guinea-pig submucous plexus

Varicosities immunoreactive for nitric oxide synthase (NOS) make synaptic connections with submucosal neurons in the guinea-pig small intestine, but the effects of nitric oxide (NO) on these neurons are unknown. We used intracellular recording to characterize effects of sodium nitroprusside (SNP, NO donor) and nitro-l-arginine (NOLA, NOS inhibitor), on inhibitory synaptic potentials (IPSPs), slow excitatory synaptic potentials (EPSPs) and action potential firing in submucosal neurons of guinea-pig ileum in vitro. Recordings were made from neurons with the characteristic IPSPs of non-cholinergic secretomotor neurons. SNP (100 μM) markedly enhanced IPSPs evoked by single stimuli applied to intermodal strands and IPSPs evoked by trains of 2–10 pulses (30 Hz). Both noradrenergic (idazoxan-sensitive) and non-adrenergic (idazoxan-insensitive) IPSPs were affected. SNP enhanced hyperpolarizations evoked by locally applied noradrenaline or somatostatin. SNP did not affect slow EPSPs evoked by single stimuli, but depressed slow EPSPs evoked by stimulus trains. NOLA (100 μM) depressed IPSPs evoked by one to three stimulus pulses and enhanced slow EPSPs evoked by trains of two to three stimuli (30 Hz). SNP also increased the number of action potentials and the duration of firing evoked by prolonged (500 or 1000 ms) depolarizing current pulses, but NOLA had no consistent effect on action potential firing. We conclude that neurally released NO acts post-synaptically to enhance IPSPs and depress slow EPSPs, but may enhance the intrinsic excitability of these neurons. Thus, NOS neurons may locally regulate several secretomotor pathways ending on common neurons.

Mechanisms of metabotropic glutamate receptor‐mediated synaptic signalling in cerebellar Purkinje cells

AbstractThe metabotropic glutamate receptors type 1 (mGluR1s) are required for a normal function of the mammalian cerebellum. These G‐protein‐coupled receptors are abundantly expressed in the principle cerebellar cells, namely the Purkinje neurones. Under physiological conditions, mGluR1s are activated during repetitive activity of both afferent glutamatergic synaptic inputs provided by the climbing and parallel fibres respectively. Unlike the common ionotropic glutamate receptors that underlie rapid synaptic excitation, mGluR1s produce a complex post‐synaptic response consisting of a Ca2+‐release signal from intracellular stores and a slow excitatory post‐synaptic potential. While it is well established that the mGluR1‐dependent Ca2+‐release signal from intracellular stores involves the activation of inositol‐trisphosphate receptors, the mechanisms underlying the slow synaptic excitation remained unclear. Here we will review recent evidence indicating an essential role of C‐type transient receptor potential (TRPC) cation channels, especially that of the subunit TRPC3, for the generation of the mGluR1‐dependent synaptic current. For the signalling pathways underlying both, Ca2+‐release from intracellular stores and the slow synaptic potential, we present current knowledge about the activators, downstream effectors and possible roles for mGluR1‐dependent signalling in Purkinje neurones.

TRPC3 Channels Are Required for Synaptic Transmission and Motor Coordination

In the mammalian central nervous system, slow synaptic excitation involves the activation of metabotropic glutamate receptors (mGluRs). It has been proposed that C1-type transient receptor potential (TRPC1) channels underlie this synaptic excitation, but our analysis of TRPC1-deficient mice does not support this hypothesis. Here, we show unambiguously that it is TRPC3 that is needed for mGluR-dependent synaptic signaling in mouse cerebellar Purkinje cells. TRPC3 is the most abundantly expressed TRPC subunit in Purkinje cells. In mutant mice lacking TRPC3, both slow synaptic potentials and mGluR-mediated inward currents are completely absent, while the synaptically mediated Ca2+ release signals from intracellular stores are unchanged. Importantly, TRPC3 knockout mice exhibit an impaired walking behavior. Taken together, our results establish TRPC3 as a new type of postsynaptic channel that mediates mGluR-dependent synaptic transmission in cerebellar Purkinje cells and is crucial for motor coordination.

α-adrenergic modulation and slow synaptic potentials in functional subclasses of paravertebral rat sympathetic neurons

α-adrenergic modulation and slow synaptic potentials in functional subclasses of paravertebral rat sympathetic neurons

Endogenous Regulator of G-Protein Signaling Proteins Regulate the Kinetics of Gαq/11-Mediated Modulation of Ion Channels in Central Nervous System Neurons

Slow synaptic potentials are generated when metabotropic G-protein-coupled receptors activate heterotrimeric G-proteins, which in turn modulate ion channels. Many neurons generate excitatory postsynaptic potentials mediated by G-proteins of the Galphaq/11 family, which in turn activate phospholipase C-beta. Accessory GTPase-activating proteins (GAPs) are thought to be required to accelerate GTP hydrolysis and rapidly turn off G-proteins, but the involvement of GAPs in neuronal Galphaq/11 signaling has not been examined. Here, we show that regulator of G-protein signaling (RGS) proteins provide necessary GAP activity at neuronal Galphaq/11 subunits. We reconstituted inhibition of native 2-pore domain potassium channels in cerebellar granule neurons by expressing chimeric Galpha subunits that are activated by Galphai/o-coupled receptors, thus bypassing endogenous Galphaq/11 subunits. RGS-insensitive variants of these chimeras mediated inhibition of potassium channels that developed and recovered more slowly than inhibition mediated by RGS-sensitive (wild-type) chimeras or native Galphaq/11 subunits. These changes were not accompanied by a change in agonist sensitivity, as might be expected if RGS proteins acted primarily as effector antagonists. The slowed recovery from potassium channel inhibition was largely reversed by an additional mutation that mimics the RGS-bound state. These results suggest that endogenous RGS proteins regulate the kinetics of rapid Galphaq/11-mediated signals in central nervous system neurons by providing GAP activity.

High-Fidelity Transmission Acquired via a Developmental Decrease in NMDA Receptor Expression at an Auditory Synapse

Central auditory relay synapses in mature animals follow high-frequency inputs for computation of sound localization. In immature mice, however, transmission at the calyx of Held synapse in auditory brainstem was inaccurate for high-frequency inputs because the summed slow synaptic potential components caused aberrant firings or blocked action potentials. As the mice matured, synaptic potentials became shorter, with smaller and faster NMDA receptor components, thereby establishing the precise one-to-one transmission for high-frequency inputs. Developmental acquisition of this high-fidelity transmission could be mimicked experimentally in immature mice by blocking NMDA receptors with d(-)2-amino-5-phosphonovaleric acid (d-APV). Furthermore, bilateral cochlear ablations at postnatal day 7 (P7) attenuated the developmental decrease of NMDA receptor expression and prevented the acquisition of high-fidelity transmission. We suggest that auditory activity, which begins at P10-P12 in mice, downregulates the expression of postsynaptic NMDA receptors, thereby contributing to the establishment of high-fidelity synaptic transmission.

PGE2 hyperpolarizes gallbladder neurons and inhibits synaptic potentials in gallbladder ganglia.

Gallbladder prostaglandin E2 (PGE2) levels are significantly elevated in pathophysiological conditions, resulting in changes in gallbladder motility or secretion that may involve actions of the prostanoid in intramural ganglia. This study was undertaken to examine the effects of PGE2 on neurons of the intramural ganglia of the guinea pig gallbladder. Application of PGE2 by microejection or superfusion elicited a complex triphasic change in the resting membrane potential (RMP). For example, application of PGE2 by microejection (100 microM) resulted in a brief hyperpolarization (mean duration 11.1 +/- 1.3 s), followed by a mid-phase repolarization toward or above RMP (mean duration 50.7 +/- 8.1 s), and finally a long-lasting hyperpolarization (mean duration 157.3 +/- 36.7 s). Associated with these PGE2-evoked alterations in RMP were changes in input resistance measured via injection of hyperpolarizing current pulses. An examination of the action potential afterhyperpolarization (AHP) during the PGE2-evoked response revealed an attenuation of both the amplitude and duration of the AHP. However, only a slight increase in excitability of gallbladder neurons in the presence of PGE2 was evident in response to depolarizing current pulses, and PGE2 did not cause the cells to fire spontaneous action potentials. Application of PGE2 reduced the amplitudes of both fast and slow excitatory synaptic potentials. These results suggest that increased prostaglandin production may decrease ganglionic output and therefore contribute to gallbladder stasis.

Electrophysiological properties of neurones in the internal and external submucous plexuses of newborn pig small intestine.

1. Intracellular microelectrodes were used to identify three major electrophysiological categories of neurone in both the internal and external submucous plexuses of the porcine small intestine. 2. Two classes of neurone with a long-lasting after-hyperpolarization following their action potential were differentiated by the presence or absence of fast excitatory synaptic inputs (EPSPs) and were termed AH neurones. S neurones received fast EPSPs but did not display after-hyperpolarizations. 3. The mean resting membrane potentials of the three groups of neurones showed a similar trend in both plexuses, with significantly higher values for the two populations of AH neurone than for S neurones. No significant variation of input resistance with cell type was detected. Neuronal input resistance was significantly greater in the internal submucous plexus than in the external submucous plexus. 4. Over 80% of AH neurones in the internal submucous plexus displayed fast EPSPs but a similar percentage of AH neurones in the external submucous plexus did not show fast EPSPs. S neurones constituted 60% of cells studied in the internal submucous plexus but less than 30% of the cell population in the external submucous plexus. 5. This study of porcine submucous neurones has revealed both similarities and differences to previous work in the guinea-pig small intestine. The most contrasting features are the relative abundance and subclassification of AH neurones in the pig in addition to the apparent paucity of slow synaptic potentials. The differences in the neuronal profiles of the internal and external submucous plexuses may reflect a differentiation of function between the two enteric nerve networks.

NMDA receptor-independent mechanisms responsible for the rate of rise of cumulative depolarization evoked by trains of dorsal root stimuli on rat spinal motoneurones

The mechanisms responsible for the rate of rise (RR) of cumulative depolarization induced by dorsal root stimulus trains were investigated with intracellular recordings from motoneurones of the rat isolated spinal cord. The NMDA receptor antagonists CPP or APV depressed the cumulative depolarization but not its RR which could still be fast enough to elicit action potential wind-up. RR size was correlated with a slow synaptic potential (detected in CPP or APV solution) with which it shared similar voltage dependence. The NK1 antagonist SR 140333 depressed cumulative depolarization, RR and slow synaptic potentials. It appears that the RR (and the ability to express wind-up) was determined by summation of slow synaptic potentials partly mediated via activation of NK1 receptors.

Dopamine directly activates a ligand-gated channel in snail neurones.

Synaptically released dopamine is known to evoke fast as well as slow synaptic potentials in neurones of gastropod molluscs. Here evidence is presented that the fast excitatory response to dopamine is mediated by the direct activation of a ligand-gated channel: unitary currents were observed in outside-out patches of neurones exposed to dopamine, and the response persisted in the presence of intracellular guanosine 5'-o-(2-thiobiphosphate), GDP[beta-S], a condition known to block G-protein-coupled responses to dopamine and other agents. In whole-cell recordings, the fast response desensitized very rapidly; it was less desensitized in outside-out patches, suggesting dependence of desensitization on an intracellular factor. The response to dopamine was blocked by D-tubocurarine and strychnine (both probably by channel blockade), by apomorphine, chlorpromazine and relatively high doses of (+/-)-sulpiride and spiperone. The channel conducts predominantly monovalent cations. Unexpectedly, the fast response to dopamine was also observed in an identified dopaminergic neurone when maintained in isolation in culture. The receptors on the dopaminergic neurone were unevenly distributed, being more abundant on the axon-hillock, axon and neurite terminals.

Intracellular recordings from intramural neurons in the guinea pig urinary bladder.

1. Intracellular recordings were made from intramural neurons in the urinary bladder of guinea pigs. 2. The neurons were located in two types of ganglia: those where the cells were densely packed and those where the neurons were loosely packed. Staining of the cells by intracellular injections of markers showed that the cells had between one to three long processes and several short dendrites. 3. The resting potential measured in 230 neurons was -55.20 +/- 0.67 (SE) mV, and the input resistance was 58.37 +/- 1.78 M omega. 4. Injection of depolarizing currents from the recording electrode evoked two types of firing patterns. In 86.2% of the neurons, depolarizing currents evoked a prolonged firing of action potentials (tonic cells). In the rest of the neurons, a depolarization elicited one to three action potentials only (phasic cells). In all the cells tested, the action potentials were reversibly blocked by tetrodotoxin (TTX; 1 microM). In the presence of TTX. Ca2+ spikes were observed in 50% of the cases. 5. Single action potentials were followed by fast hyperpolarizations having mean duration of 92.7 +/- 6.0 ms and amplitude of 13.3 +/- 1.0 mV. In 62.5% of the cells repetitive firing of action potentials was followed by delayed, slow hyperpolarizations (duration 3.8 +/- 0.5 s), which were diminished by the K+ channel blocker 4-aminopyridine and in Ca+2-free high-Mg2+ medium. These results indicate that the prolonged after-spike hyperpolarizations were due to opening of Ca(2+)-induced K+ channels. 6. Electrical stimulation of nerve fiber tracts evoked fast excitatory synaptic potentials that were blocked by the nicotinic receptor antagonist hexamethonium (0.2 mM). Exogenous acetylcholine elicited depolarizations that were also blocked by hexamethonium. Nerve stimulation at frequencies of 0.1 Hz or higher caused strong facilitation of the synaptic potentials. Stimulation at 10-20 Hz did not evoke slow synaptic potentials.

Effects of 5-HT 1A and 5-HT 4 receptor agonists on slow synaptic potentials in enteric neurons

Intracellular electrophysiological methods were used to examine the effects of 5-hydroxytryptamine (5-HT), 5-carboxa-midotryptamine (5-CT), 5-methoxytryptamine (5-MeOT), 4-amino-5-chloro-2-methoxy- N-(4-[1-azabicyclo3,3,1]nonyl]) benzamide hydrochloride (renzapride), cis-4-amino-5-chloro- N[1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidiny]-2-methoxybenzamide monohydrate (cisapride) and endo- N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-3-(1-methyl)ethyl-2-oxo-1H-benzimidazole-1-carboxamidehydrochloride (BIMU 8) on noncholinergic slow excitatory postsynaptic potentials (slow EPSPs) in myenteric afterhyperpolarization (AH) neurons of guinea pig ileum. 5-HT (0.01–1 μM) and 5-CT (0.001–0.1 μM) produced a concentration-dependent inhibition of slow EPSPs. The 5-HT 1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimidobutyl]piperazine (NAN-190) produced rightward shifts in 5-HT and 5-CT concentration-response curves; facilitation of slow EPSPs was never observed. 5-MeOT caused a depolarization and inhibited spike afterhyperpolarizations in a concentration-dependent manner but this effect was not blocked by the 5- HT 3 5- HT 4 receptor antagonist, tropisetron (1 μM). Renzapride (0.01–0.3 μM), cisapride (0.01–1.0 μM) and BIMU 8 (0.01–1.0 μM) did not change the membrane potential of any neuron tested. Renzapride and BIMU 8 did not change the amplitude of slow EPSPs. In 13 of 19 neurons cisapride did not change the amplitude of slow EPSPs; in 6 neurons cisapride (1 μM) reversibly inhibited the slow EPSP. Responses to substance P which mimicked the slow EPSP were not affected by cisapride. These data indicate that excitatory 5-HT 4 receptors are not localized to cell bodies of AH neurons and are not coupled to presynaptic facilitation of noncholinergic slow EPSPs in AH neurons.

Activation of calcium-dependent chloride channels causes post-tetanic depolarization in rabbit parasympathetic neurons

Intracellular recordings were made from neurons in rabbit and feline vesical parasympathetic ganglia in vitro. In response to cathodal current injection (0.1–1 nA for 2–20 ms) the majority of rabbit neurons (229 out of 250) exhibited a single action potential that was followed by a fast and slow after-hyperpolarization (sAHP neuron). The remainder of the cells exhibited an action potential followed by only a fast after-hyperpolarization (fAHP neuron). fAHP neurons did not exhibit anomalous rectification and a spontaneous rhythmic hyperpolarization, which were common membrane properties in sAHP neurons. In response to a train of cathodal current pulses (5–20 Hz for 0.1–10 s), fAHP neurons exhibited action potentials followed by a post-tetanic depolarization (PTD). The PTD was associated with a decrease in membrane input resistance. The amplitude and duration of the PTD were a function of the number of action potentials in the train. The amplitude of the PTD was increased by membrane hyperpolarization and its estimated reversal potential was approximately −30 mV. Low-chloride solution and intracellular injection of chloride ions augmented the amplitude and duration of the PTD, whereas low-sodium, high-potassium and low-potassium solutions did not affect them. Tetraethylammonium (5–10 mM) and barium (0.5–1 mM) increased the amplitude and duration of the PTD. Nominal calcium-free solutions and ω-conotoxin (500 nM) abolished the PTD. The data suggest that activation of chloride channels by calcium influx through ω-conotoxin-sensitive calcium channels mediates the PTD. Repetitive stimulation of the pelvic nerve evoked a train of orthodromic action potentials followed by the PTD of fAHP neurons. (+)-Tubocurarine (10 μM) and hexamethonium (200 μM), but not atropine (1 μM), abolished orthodromic action potentials and the PTD, whereas these cholinergic antagonists did not depress the PTD evoked by direct action potentials. In summary, the data suggest that the PTD may function as a slow synaptic potential in fAHP neurons. This appears likely because neither slow excitatory nor inhibitory postsynaptic potentials are present in neurons of rabbit vesical parasympathetic ganglia. In contrast, slow inhibitory and excitatory postsynaptic potentials were recorded from neurons in feline vesical parasympathetic ganglia.

Morphine Selectively Depresses the Slowest, NMDA‐independent Component of C‐fibre‐evoked Synaptic Activity in the Rat Spinal Cord In Vitro

The effects of morphine on the depolarizing synaptic responses produced in motoneurons by electrical stimulation of primary sensory neurones have been recorded in hemisected spinal cord preparations (8- to 12-day-old rat pups). Morphine at concentrations of 0.1-20 microM reduced a slow, long-lasting (latency greater than 1 s, duration up to 10 s) component of the ventral root potential (VRP) evoked by C-fibre strength stimulation of the dorsal root. At 2 microM the reduction in area of this slow synaptic potential was 71.7 +/- 0.9% of control values (n = 15). The earliest components of the C-fibre strength VRP (the first 100 ms) and the responses to A beta strength stimuli were unaffected by the opioid even at 10-20 microM. The intermediate, NMDA receptor antagonist (D-AP5, 40 microM)-sensitive component (which lasts 100-1000 ms) was reduced by 34 +/- 2.2% of control (n = 15), which was significantly less than the reduction of the later NMDA-independent component (P < 0.001). Morphine (0.1-20 microM) also depressed the cumulative depolarization generated by the temporal summation of synaptic responses evoked by brief trains of C-fibre strength stimuli (1 or 10 Hz). A significantly greater reduction at the lower frequency of stimulation (56.3 +/- 2.0%) than at the higher (20.3 +/- 1.69%, n = 10, measured at 2 microM morphine) was found (P < 0.005). The effects of morphine were reversible upon wash-out or superfusion with the opioid receptor antagonist naloxone (2 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

NK1 and NK2 receptors contribute to C-fibre evoked slow potentials in the spinal cord.

Small diameter primary afferents produce slow synaptic potentials in spinal neurones. These can be recorded as prolonged ventral root potentials (VRPs) in the isolated neonatal rat spinal cord preparation. The VRP elicited by stimulating C-fibres consists of two phases: an early phase comprising a monosynaptic and a short polysynaptic response identical to that elicited by low threshold A beta fibres and a late phase which has an initial component (0.1-1 s) which is sensitive to N-methyl-D-aspartic acid receptor antagonism and a very long lasting second component (1-20 s) which is resistant to these antagonists. We now demonstrate that the slowest component of the VRP is significantly reduced by both NK1 and NK2 tachykinin receptor antagonists and as a consequence, tachykinins have a particular contribution to the cumulative depolarization produced by low frequency (1 Hz) C-fibre stimulation.

Lemniscal and non-lemniscal synaptic transmission in rat auditory thalamus.

1. The central auditory pathway linking the inferior colliculus (IC) and the medial geniculate body (MGB) of the thalamus consists of a segregated ventral lemniscal and dorsal non-lemniscal projection whose synaptic transmission mechanisms remain unknown. Extracellular and intracellular recordings combined with axonal tract tracing and cell staining were made from lemniscal and non-lemniscal divisions of adult rat MGB maintained acutely in in vitro explants containing parallel tectothalamic projections. 2. Biocytin deposition within the brachium of the IC revealed dense axonal fibres projecting to the MGB. Thin axonal terminals were found throughout the ventral (MGv) and dorsal (MGd) divisions of the MGB. Bushy cells with tufted or bitufted dendritic branches were primarily found in the MGv. In the MGd, cells were mainly seen as stellate neurones having a radiate dendritic arbor. 3. Electrical stimulation of the brachium of IC invariably elicits fast, excitatory synaptic potentials in both MGv and MGd cells. The evoked responses occurred monosynaptically and were exclusively mediated by glutamate acting on both N-methyl-D-aspartate (NMDA) and non-NMDA receptors. Non-lemniscal MGd neurones recorded extracellularly exhibited a strong tendency to discharge in bursts in response to brachium stimulation. In contrast, a large proportion of ventral lemniscal cells tended to discharge in single or dual spikes. Intracellularly, MGd cells, but not MGv cells, showed a predominant, slow synaptic potential mediated by NMDA receptors. 4. It is concluded that the central auditory circuitry linking the tectum and the thalamus is connected monosynaptically via glutamatergic synapses. Lemniscal and non-lemniscal thalamic neurones possess distinct response properties which cannot be accounted for by a differential transmitter system or polysynaptic delays as postulated previously.

Nicotinic and muscarinic synaptic transmission in canine intracardiac ganglion cells innervating the sinoatrial node

Nicotinic and muscarinic mediated synaptic mechanisms were investigated in isolated, canine intracardiac ganglia taken from the right atrial fat pad. Using conventional intracellular microelectrode recording techniques on 216 neurons fast, and slow synaptic potentials were evoked by single or trains of stimulation of presynaptic fibers in interganglionic nerves. By varying the stimulus intensity, single or multiple fast excitatory postsynaptic potentials (f-EPSPs) were evoked, indicating the convergence of synaptic inputs on these cells. These f-EPSPs often reached the action potential threshold, were enhanced by the acetelcholinesterase inhibitor physostigmine and were blocked by the nicotinic antagonist hexamethonium. The f-EPSPs were accompanied by a decreased input resistance and had an extrapolated reversal potential of −7.1 mV, suggesting increased conductances to more than one cation. Repetitive presynaptic stimulation evoked slow excitatory postsynaptic potentials (s-EPSPs) in 41% of the cells while slow inhibitory postsynaptic potentials (s-IPSPs) or s-IPSPs followed by s-EPSPs were evoked in 19% of the cells. All slow potentials were abolished by atropine and low Ca 2+/high Mg 2+ solutions and enhanced by physostigmine. Hexamethonium and adrenergic receptor antagonists had no effects on s-EPSP and s-IPSP. The M 1 receptor antagonist pirenzepine reversibly blocked the s-EPSP but not the s-IPSP. On the other hand, the M 2 receptor blocker 4-diphenyl-acetoxy- N-methyl piperidine methiodide (4-DAMP) had no effects on the s-EPSP. These observations suggest that s-EPSPs and s-IPSPs are mediated by distinct muscarinic by increased input resistance. These responses were decreased in amplitude by membrane hyperpolarization and either reversed polarity or declined to zero amplitude at about −80 mV, suggesting the inhibition of a potassium conductance.