Biomedical subjects

P Sah

Publications and source records attributed to P Sah.

At least 37 records · Page 2Linked to original sources

PubMed1997

The removal of acetylcholine by diffusion at nicotinic synapses in the rat otic ganglion.

1. We have examined the clearance of synaptically released acetylcholine in the otic ganglion when acetylcholinesterase was blocked with eserine. 2. Intracellular recordings were made from otic ganglion neurones, in vitro. The decay of the excitatory postsynaptic potential (EPSP), in response to stimulation of afferent fibres, was greatly prolonged in the presence of eserine. Low frequency (0.05-4 Hz) repetitive synaptic stimulation led to a slow depolarization of the postsynaptic cell that persisted throughout the period of stimulation. This slow depolarization was blocked by the nicotinic antagonists mecamylamine (100 microM) or (+)tubocurarine (100 microM), but was unaffected by atropine (1 microM), indicating that the response was due to the activation of nicotinic receptors. 3. Following 2 Hz synaptic stimulation (30 s), the rate of rise of the slow depolarization had a time constant of 3.1 +/- 0.4 s and a peak amplitude of 12 +/- 1 mV. Upon cessation of stimulation, the depolarization decayed to resting levels with a time constant of 18.3 +/- 1.5 s (n = 23). At increasing stimulation frequencies the rate of rise of the depolarization increased. Lowering the probability of release, by adding cadmium to the perfusing solution or by lowering extracellular calcium, slowed the rise time of the response. 4. Both the onset and decay kinetics of the slow depolarization had a low temperature sensitivity, indicating that they reflect diffusional processes. 5. Repetitive stimulation (2 Hz) of the afferent nerve supplying the ganglion, in the presence of eserine, also caused a slow depolarization in cell in which we could not demonstrate a synaptic input. This indicates that synaptically released acetylcholine can spill over onto nearby neurones. 6. We conclude that at parasympathetic synapses, under physiological conditions, transmitter action is terminated by the enzymatic degradation of acetylcholine. When acetylcholinesterase is blocked, acetylcholine accumulates because its removal by diffusion is slow.

Acetylcholine↗

PubMed1997

Ca(2+)-activated K+ channels in rat otic ganglion cells: role of Ca2+ entry via Ca2+ channels and nicotinic receptors.

1. Intracellular recordings were made from neurones in the rat otic ganglion in vitro in order to investigate their morphological, physiological and synaptic properties. We took advantage of the simple structure of these cells to test for a possible role of calcium influx via nicotinic acetylcholine receptors during synaptic transmission. 2. Cells filled with biocytin comprised a homogeneous population with ovoid somata and sparse dendritic trees. Neurones had resting membrane potentials of -53 +/- 0.7 mV (n = 69), input resistances of 112 +/- 7 M omega, and membrane time constants of 14 +/- 0.9 ms (n = 60). Upon depolarization, all cells fired overshooting action potentials which were followed by an apamin-sensitive after-hyperpolarization (AHP). In response to a prolonged current injection, all neurones fired tonically. 3. The repolarization phase of action potentials had a calcium component which was mediated by N-type calcium channels. Application of omega-conotoxin abolished both the repolarizing hump and the after-hyperpolarization suggesting that calcium influx via N-type channels activates SK-type calcium-activated potassium channels which underlie the AHP. 4. The majority (70%) of neurones received innervation from a single preganglionic fibre which generated a suprathreshold excitatory postsynaptic potential mediated by nicotinic acetylcholine receptors. The other 30% of neurones also had one or more subthreshold nicotinic inputs. 5. Calcium influx via synaptic nicotinic receptors contributed to the AHP current, indicating that this calcium has access to the calcium-activated potassium channels and therefore plays a role in regulating cell excitability.

Animals↗

PubMed1996

Apical dendritic location of slow afterhyperpolarization current in hippocampal pyramidal neurons: implications for the integration of long-term potentiation.

Trains of action potentials in hippocampal pyramidal neurons are followed by a prolonged afterhyperpolarization (AHP) lasting several seconds, which is attributable to the activation of a slow calcium-activated potassium current ((sI)AHP). Here we examine the location of (sI)AHP on CA1 pyramidal neurons by comparing it with two GABAergic inhibitory postsynaptic currents (IPSCs) with known somatic and dendritic locations. Whole-cell patch-clamp recordings were made for CA1 pyramidal neurons in acute hippocampal slices. Stepping the membrane potential at the peak of (sI)AHP produced a relaxation ("switchoff") of the AHP current with a time constant of 7.4 +/- 0.4 msec (mean +/- SEM). The switchoff time constants for somatic and dendritic GABAA IPSCs were 3.5 +/- 0.5 msec and 8.8 +/- 0.3 msec, respectively. This data, together with cable modeling, indicates that active (sI)AHP channels are distributed over the proximal dendrites within approximately 200 micrometers of the soma. Excitatory postsynaptic potentials (EPSPs) evoked in stratum (s.) radiatum had their amplitudes shunted more by the AHP than did EPSPs evoked in s. oriens, suggesting that active AHP channels are restricted to the apical dendritic tree. Blockade of the AHP during a tetanus, which in control conditions elicited a decremental short-term potentiation (STP), converted STP to long-term potentiation (LTP). Thus, activation of the AHP increases the threshold for induction of LTP. These results suggest that in addition to its established role in spike frequency adaptation, the AHP works as an adjustable gain control, variably hyperpolarizing and shunting synaptic potentials arising in the apical dendrites.

Action Potentials↗

PubMed1996

Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation.

Action potentials in neurones are followed by a hyperpolarization, which can last up to several seconds. This hyperpolarization has several phases that are mediated by the activation of different types of Ca(2+)-activated K+ currents. Patch-clamp studies have revealed two families of Ca(2+)-activated K+ channels of small (SKCa) and high (BKCa) conductance. Activation of BKCa channels contributes to action-potential repolarization, while SKCa channels are thought to underlie the afterhyperpolarization (AHP). In addition, AHPs in neurones can be divided into two distinct types that are easily separated by kinetic and pharmacological criteria. It is now clear that only one type of AHP can be explained by activation of SKCa channels while a new type of Ca(2+)-activated K+ channel underlies the other. Modulation of this channel by a range of transmitters is a key determinant of the excitability of many neurones.

Calcium↗

PubMed1995

Membrane properties and synaptic potentials in rat sympathetic preganglionic neurons studied in horizontal spinal cord slices in vitro.

Intracellular recordings were made from neurons in the intermediolateral column and adjacent white matter in horizontal slices of upper thoracic spinal cord from rats aged 21-28 days. Membrane properties were studied in the presence of picrotoxin (100 microM) to block ongoing inhibitory synaptic potentials. 37 neurons were identified as sympathetic preganglionic neurons (SPNs) by their electrical behaviour, anatomical location and/or morphology. SPNs had resting potentials of -57 +/- 2 mV and input resistances of 254 +/- 31 M omega (n = 14). Following a hyperpolarising voltage step, a transient outward current was activated which had a time constant of decay of approx. 400 ms. The inflection in the repolarising phase of the action potential and the following prolonged AHP were both abolished by Cd2+ (50 microM). The current underlying the AHP had two components with kinetic properties similar to the two calcium-activated potassium conductances, gKCa1, and gKCa2, characterized in other autonomic neurons. Noradrenaline (10-100 microM) caused a small depolarization and blocked the calcium component of the action potential suppressing the AHP. This revealed an afterdepolarization (ADP) with an underlying inward current with a decay time constant of approx. 150 ms. All effects of noradrenaline were blocked by phentolamine (10 microM). Graded stimulation of the lateral funiculus 0.5-1 mm rostral to the recording site evoked in all cells monosynaptic fast excitatory synaptic potentials (fEPSPs) which were graded in amplitude. fEPSPs decayed with a time constant identical to the cell input time constant and were reduced in amplitude by CNQX (10-20 microM). In 7 cells, higher stimulus voltages elicited slow EPSPs with a time to peak of 1.1 +/- 0.1 s and a half decay of 2.8 +/- 0.3 s (n = 7) which were not reduced by alpha-adrenoceptor antagonists. The AHP was not blocked when the action potential was initiated during the slow EPSP. We conclude that excitatory bulbospinal inputs to SPNs involve at least one fast transmitter which is likely to be glutamate and one slow transmitter which is not noradrenaline.

Action Potentials↗

PubMed1995

Different calcium channels are coupled to potassium channels with distinct physiological roles in vagal neurons.

Whole-cell and sharp microelectrode recordings were obtained from neurons of rat dorsal motor nucleus of the vagus (DMV) in transverse slices of the rat medulla maintained in vitro. Calcium currents were studied with sodium currents blocked with tetrodotoxin, potassium currents blocked by perfusing the cell with caesium as the main cation and using barium as the charge carrier. From a holding potential of -60 mV, inward currents activated at potentials positive of -50 mV and peaked around 0 mV. Voltage clamping the neuron at more hyperpolarised potentials did not reveal any low-threshold inward current. The inward current was effectively blocked by cadmium (100 microM) and nicked (1 mM), suggesting that it is carried by voltage-dependent calcium channels. The inward current could be separated into three pharmacologically distinct components: 40% of the whole cell current was omega-conotoxin sensitive; 20% of the current was nifedipine sensitive; and the rest was blocked by high concentrations of cadmium and nickel. This remaining current cannot be due to P-type calcium channels as omega-agatoxin had no effect on the inward current. Nifedipine had no significant effect on the action potential. Application of omega-conotoxin reduced the calcium component of the action potential and significantly reduced the potassium current underlying the afterhyperpolarization. Application of charybdotoxin slowed action potential repolarization. When N-type calcium channels were blocked with omega-conotoxin, charybdotoxin was still effective in slowing repolarization. In contrast, charybdotoxin was ineffective ineffective when calcium influx was blocked with the non-specific calcium channel blocker cadmium.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1995

Channels underlying the slow afterhyperpolarization in hippocampal pyramidal neurons: neurotransmitters modulate the open probability.

The slow afterhyperpolarization in hippocampal pyramidal neurons is mediated by a calcium-activated potassium current (IAHP) and is a target for variety of different neurotransmitters. The characteristics of the channels underlying IAHP and how they are modulated by neurotransmitters are, however, unknown. In this study, we have examined the properties of the channels underlying IAHP using fluctuation analysis of the macroscopic current. Our results indicate that this channel has a unitary conductance of 2-5 pS and a mean open time of about 2 ms. When the peak amplitude of IAHP was maximal, these channels have an open probability of 0.4. Noradrenaline and carbachol reduced IAHP amplitude by lowering open channel probability. These result indicate that a novel calcium-activated potassium channel underlies IAHP. This channel is modulated in a similar fashion by two different transmitter systems that utilize distinct protein kinases.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1995

Properties of channels mediating the apamin-insensitive afterhyperpolarization in vagal motoneurons.

1. Whole cell recordings were obtained from neurons of the dorsal motor nucleus of the vagus in transverse slices of guinea pig medulla. From a holding potential of -40 mV, short depolarizing voltage steps activated two calcium-dependent potassium currents, Gk(Ca),1 and Gk(Ca),2. 2. Gk(Ca),1 was completely blocked by apamin (100 nM). Gk(Ca),2 was apamin insensitive, voltage independent, and reversed close to the potassium equilibrium potential. 3. Activation of Gk(Ca),2 was associated with an increase in current variance. The channels underlying the slow component were analyzed by stationary and nonstationary fluctuation analysis. Current variance was linearly related to mean current for small current amplitudes but clearly deviated from linearity near the peak of Gk(Ca),2. The predicted single channel conductance was 6.8 +/- 2.5 (SE) pS. Probability of channel opening rose to at most 0.68. The average number of available Gk(Ca),2 channels on vagal neurons was 4,437 +/- 591. 4. Power spectra were constructed from the peak current. Spectra were well fitted with a single Lorentzian with a corner frequency of 72 +/- 7 Hz. The mean burst duration of the channels was 3.8 +/- 0.5 ms. These results indicate that a new type of calcium-activated channel underlies Gk(Ca),2.

Animals↗

PubMed1994

Subcellular distribution of ryanodine receptor-like and calcium ATPase-like immunoreactivity in brainstem and cerebellar neurones of rat and guinea pig.

Monoclonal antibodies against ryanodine receptor (5C3) and calcium ATPase (D12) of skeletal muscle sarcoplasmic reticulum were used in an immunoelectron microscopic study of cerebellar Purkinje cells and neurons of the hypoglossal and dorsal motor nuclei of the vagus (DMV) from rat and guinea-pig. All neurones were labelled with D12 and all, except rat DMV, labelled with 5C3. Most labelling was on smooth endoplasmic reticulum within 500 nm of the plasmalemma where Ca(2+)-activated Ca2+ release would rapidly increase cytosolic calcium following a small Ca2+ influx across the plasmalemma.

Animals↗

PubMed1993

Differences in electrophysiological properties between neurones of the dorsal motor nucleus of the vagus in rat and guinea pig.

We have examined the electrophysiological properties of neurones in the dorsal motor nucleus of the vagus (DMV) in rats and guinea pigs in transverse medullary slices maintained in vitro. There were only minor differences in the morphology of the neurones between the species, and their passive electrical properties were very similar. However, action potentials in guinea pig neurones had larger amplitudes and longer half-widths than did those in rat neurones. In both species, action potentials were followed by prolonged afterhyperpolarisations (AHPs). In the majority of guinea pig neurones, two calcium-activated potassium currents underlying the AHP could be separated into an early apamin-sensitive component and a late apamin-insensitive component. In rat neurones, the current underlying the AHP was briefer and entirely apamin-sensitive. In response to a step of depolarising current, neurones in the guinea pig only discharged once or twice and then ceased firing. In rat neurones, this manoeuvre produced repetitive firing. An inward rectifier was larger in neurones of the guinea pig than in those in the rat. The effects of 5-hydroxytryptamine and noradrenaline also differed between neurones of each species. We conclude that, despite many similarities of size and electrical properties, DMV neurones in the two species differ in terms of several voltage- and calcium-dependent conductances which determine their active electrical behaviour.

Animals↗

PubMed1993

Calcium induced calcium release is involved in the afterhyperpolarization in one class of guinea pig sympathetic neurone.

The mechanisms underlying two potassium conductances which are activated by Ca2+ influx during the action potential in sympathetic prevertebral neurones of guinea pigs have been investigated pharmacologically. One Ca-activated K+ conductance, which is present in all mammalian sympathetic postganglionic neurones, is maximal after the action potential and decays exponentially with a time constant of about 130 ms; this conductance was inhibited by apamin (50-100 nM) consistent with the involvement of SK channels. A second Ca-activated K+ conductance with much slower kinetics is present in a large subpopulation of coeliac neurones. This conductance was resistant to apamin but markedly inhibited by application of ryanodine (5-20 microM), suggesting that Ca2+ influx during the action potential triggers release of Ca2+ from intracellular stores which in turn activates a different class of K+ channel. Noradrenaline (100 microM) depressed the second K+ conductance selectively.

Action Potentials↗

PubMed1993

Distribution of ryanodine receptor-like immunoreactivity in mammalian central nervous system is consistent with its role in calcium-induced calcium release.

The distributions of ryanodine receptor-like immunoreactivity and Ca-ATPase-like immunoreactivity were identified in the guinea-pig and rat central nervous system using antibodies raised against the rabbit skeletal muscle ryanodine receptor and Ca-ATPase. In both guinea-pig and rat cerebellum, the ryanodine receptor-like immunoreactivity was restricted to the soma and dendrites of Purkinje cells. In the medulla, neuron somata in the hypoglossal nucleus were stained in both species, but in the dorsal motor nucleus of the vagus somata were stained in guinea-pigs but not in rats. This species difference in ryanodine receptor-like immunoreactivity is consistent with the species difference in expression of a ryanodine sensitive, calcium activated potassium conductance in neurons of the dorsal motor nucleus of the vagus. Immunoreactivity to Ca-ATPase was present in vagal motoneurons in both species with denser staining in the guinea-pig. The data further support the idea that, in neurons of the dorsal motor nucleus of the vagus, release of intracellular calcium stores via a ryanodine receptor activates a specific class of potassium channels, thereby modulating cell excitability.

Animals↗

PubMed1993

Kinetic properties of a slow apamin-insensitive Ca(2+)-activated K+ current in guinea pig vagal neurons.

1. The calcium-activated outward current (gKCa,2) following an action potential was recorded from neurons in the guinea pig dorsal motor nucleus of the vagus (DMV). gKCa,2 was activated after a delay after the action current and had a distinct rising phase in contrast to the apamin sensitive calcium-activated current in rat DMV neurons (gKCa,1). 2. The time course of gKCa,2 was well described by function of the form A*[exp(t/tau 1)-exp(t/tau 2)], where tau 1 = 1.42 +/- 0.05 (SE) s and tau 2 = 555 +/- 24 ms. 3. Increasing calcium influx by firing multiple action currents lead to an increase in the peak amplitude of gKCa,2 with no change in its kinetics. In cells loaded with low concentrations of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), gKCa,2 was smaller in amplitude but its time course was similar to that in cells not loaded with EGTA. 4. When preceded by a conditioning influx of calcium, the amplitude and time course of gKCa,2 was identical to one with no conditioning influx. These results show that, after influx of calcium, a potassium current with stereotyped amplitude and kinetics is generated. 5. These data are consistent with the idea that the source of calcium for activation of gKCa,2 is not the extracellular space.

Action Potentials↗

PubMed1992

A slow voltage-activated potassium current in rat vagal neurons.

Potassium currents play a key role in controlling the excitability of neurons. In this paper we describe the properties of a novel voltage-activated potassium current in neurons of the rat dorsal motor nucleus of the vagus (DMV). Intracellular recordings were made from DMV neurons in transverse slices of the medulla. Under voltage clamp, depolarization of these neurons from hyperpolarized membrane potentials (more negative than -80 mV) activated two transient outward currents. One had fast kinetics and had properties similar to A-currents. The other current had an activation threshold of around -95 mV (from a holding potential -110 mV) and inactivated with a time constant of about 3s. It had a reversal potential close to the potassium equilibrium potential. This current was not calcium dependent and was not blocked by 4-aminopyridine (5 mM), catechol (5 mM) or tetraethylammonium (20 mM). It was completely inactivated at the resting membrane potential. This current therefore represents a new type of voltage-activated potassium current. It is suggested that this current might act as a brake to repetitive firing when the neuron is depolarized from membrane potentials negative to the resting potential.

4-Aminopyridine↗

PubMed1992

Potassium currents contributing to action potential repolarization and the afterhyperpolarization in rat vagal motoneurons.

1. Intracellular recordings were made from neurons in the dorsal motor nucleus of the vagus (DMV) in transverse slices of rat medulla maintained in vitro at 30 degrees C. Neurons had a resting potential of -59.8 +/- 1.4 (SE) mV (n = 39) and input resistance of 293 +/- 23 M omega (n = 44). 2. Depolarization elicited overshooting action potentials that were blocked by tetrodotoxin (TTX; 1 microM). In the presence of TTX, two types of action potentials having low and high thresholds could be elicited. The action potentials were blocked by cobalt (2 mM) indicating they were mediated by calcium currents. 3. Under voltage clamp, depolarization of the cell from membrane potentials negative of the resting potential activated a transient potassium current. This current was selectively blocked by 4-aminopyridine (4-AP) (5 mM) and catechol (5 mM) indicating that it is an A-type current. This current inactivated with a time constant of 420 ms and recovered from inactivation with a time constant of 26 ms. 4. When calcium currents were blocked by cadmium or cobalt, the rate of action potential repolarization was slower. In the presence of tetraethylammonium (TEA; 200-400 microM) or charybdotoxin (CTX; 30 nM) a small "hump" appeared on the repolarizing phase of the action potential that was abolished by addition of cadmium. These results indicate that a calcium-activated potassium current (IC) contributes to action potential repolarization. 5. Actions potentials elicited from hyperpolarized membrane potentials repolarized faster than those elicited from resting membrane potential. This effect could be blocked by catechol, indicating that voltage-dependent potassium currents (IA) can also contribute to action-potential repolarization. In the presence of catechol and calcium channel blockers, action potentials still had a significant early afterhyperpolarization suggesting that another calcium independent outward current is also active during repolarization. This fast afterhyperpolarizations (AHP) was not blocked by TEA. 6. Action potentials were followed by prolonged AHPs, which had two phases. The initial part of the AHP was blocked by apamin (100 nM) indicating that it results from activation of SK type calcium-activated potassium channels. The slow phase was selectively blocked by catechol suggesting that it is due to activation of IA. 7. It is concluded that a TTX-sensitive sodium current and two calcium currents contribute to the action potential in rat DMV neurons. At least three different currents contribute to action-potential repolarization: IC, IA, and a third unidentified calcium-insensitive outward current.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1992

Role of calcium influx and buffering in the kinetics of Ca(2+)-activated K+ current in rat vagal motoneurons.

1. Intracellular recordings were obtained from neurons of the dorsal motor nucleus of the vagus (DMV) in transverse slices of the rat medulla maintained in vitro. These neurons had a resting potential of -59.8 +/- 8.7 (SD) mV. Single action potentials elicited by brief depolarizing current pulses were followed by a prolonged afterhyperpolarization (AHP). Under voltage clamp, the current underlying the AHP was found to be a calcium-activated potassium current. 2. The outward current (GkCa,1) was voltage insensitive and was not blocked by tetraethylammonium (TEA) (10 mM). Unlike the slower time course calcium-activated potassium current recorded in some other neurons, GkCa,1 was blocked by apamin (25-100 nM), indicating that SK type calcium-activated potassium channels underlie this current. 3. GkCa,1 was maximal within 10 ms of the action potential and its decay was well described by a single exponential. After a single action potential the time constant of decay of GkCa,1 was 155 +/- 66 (+/- SD) ms. 4. Calcium influx was increased by adding TEA to the extracellular solution or by firing more than one action potential. As the calcium load was increased, both the peak amplitude and the time constant of decay of GkCa,1 increased. In cells impaled with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)-filled electrodes, the time constant of decay of GkCa,1 after a single action current was 71 +/- 19 ms. 5. A simple diffusion-based model that incorporates two intrinsic calcium buffers is developed that accounts for many of the properties of GkCa,1. It is concluded that the decay of GkCa,1 reflects the time course of removal of calcium that has entered the cell during the action potential.

Action Potentials↗

PubMed1991

Ca(2+)-activated K+ currents underlying the afterhyperpolarization in guinea pig vagal neurons: a role for Ca(2+)-activated Ca2+ release.

We examined the possibility that Ca2+ released from intracellular stores could activate K+ currents underlying the afterhyperpolarization (AHP) in neurons. In neurons of the dorsal motor nucleus of the vagus, the current underlying the AHP had two components: a rapidly decaying component that was maximal following the action potential (GkCa,1) and a slower component that had a distinct rising phase (GkCa,2). Both components required influx of extracellular Ca2+ for their activation, and neither was blocked by extracellular TEA (10 mM). GkCa,1 was selectively blocked by apamin, whereas GkCa,2 was selectively reduced by noradrenaline. The time course of GkCa,2 was markedly temperature sensitive. GkCa,2 was selectively blocked by application of ryanodine or sodium dantrolene, or by loading cells with ruthenium red. These results suggest that influx of Ca2+ directly gates one class of K+ channels and leads to release of Ca2+ from intracellular stores, which activates a different class of K+ channel.

Action Potentials↗

PubMed1991

Mechanisms underlying potentiation of synaptic transmission in rat anterior cingulate cortex in vitro.

1. The properties of the excitatory synapse made by callosal inputs onto layer V and layer VI cells in the anterior cingulate cortex were studied in an in vitro slice preparation with intracellular recording. 2. In the presence of picrotoxin, the excitatory postsynaptic potential (EPSP) had two components, a fast component blocked by the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and a slow component blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonovalerate (APV). 3. Delivery of a brief tetanus to the afferent fibres led to a long-term potentiation (LTP) of the initial slope of the monosynaptic EPSP. The LTP displayed the property of co-operativity and could be blocked by APV or by buffering intracellular calcium. 4. Pairing of low frequency presynaptic activity or weak tetanic stimulation with postsynaptic depolarization failed to potentiate the EPSP. This suggests that postsynaptic depolarization alone is unable to explain the co-operativity. 5. It is concluded that the transmitter mediating the excitatory input between callosal afferents and layer V and layer VI pyramidal neurones is glutamate. Tetanic stimulation of these afferents leads to LTP which shares many but not all the properties of LTP seen in the CA1 region of the hippocampus.

2-Amino-5-phosphonovalerate↗