Biomedical subjects

A Gelperin

Publications and source records attributed to A Gelperin.

At least 37 records · Page 2Linked to original sources

PubMed1993

Coherent network oscillations by olfactory interneurons: modulation by endogenous amines.

1. The procerebral (PC) lobe of the terrestrial mollusk Limax maximus contains a highly interconnected network of local olfactory interneurons that receives direct axonal projections from the two pairs of noses. This olfactory processing network generates a 0.7-Hz oscillation in its local field potential (LFP) that is coherent throughout the network. The oscillating LFP is modulated by natural odorants applied to the neuroepithelium of the superior nose. 2. Two amines known to be present in the PC lobe, dopamine and serotonin, increase the frequency of the PC lobe oscillation and alter its waveform. 3. Glutamate, another putative neurotransmitter known to be present in the lobe, suppresses the PC lobe oscillation by a quisqualate-type receptor and appears to be used by one of the two classes of neurons in the PC lobe to generate the basic LFP oscillation. 4. The known activation of second messengers in Limax PC lobe by dopamine and serotonin together with their effects on the oscillatory rhythm suggest the hypothesis that these amines augment mechanisms mediating synaptic plasticity in the olfactory network, similar to hypothesized effects of amines in vertebrate olfactory systems. 5. The use of a distributed network of interneurons showing coherent oscillations may relate to the highly developed odor recognition and odor learning ability of Limax.

Animals↗

PubMed1993

Cultured olfactory interneurons from Limax maximus: optical and electrophysiological studies of transmitter-evoked responses.

1. The olfactory processing network in the procerebral (PC) lobe of the terrestrial mollusk Limax maximus exhibits a coherent oscillation of local field potential that is modulated by odor input. To understand the cellular basis of this oscillation, we developed a cell culture preparation of isolated PC neurons and studied the responses of isolated cells to stimulation with neurotransmitters known to be present in the PC lobe. 2. The distribution of PC soma diameters suggests at least two different populations of neurons. Approximately 95% of isolated cells had soma diameters of 7-8 microns, with the remaining cells having larger diameters (10-15 microns). 3. Extracellular measurements of action potentials and optical measurements of intracellular calcium concentrations in fura-2-loaded cells were made. Serotonin and dopamine excited PC neurons and promoted transitions from steady to bursty activity. Both amines elicited increases in intracellular calcium, presumably concomitant with the increase in action-potential frequency. 4. Glutamate suppressed action-potential firing and reduced intracellular calcium. This effect was seen most clearly when glutamate was applied to cells excited by high potassium medium. Quisqualate is an effective glutamate agonist in this system, whereas kainate is not. 5. Combined with anatomic and biochemical data and with studies of the effects of these neurotransmitters on the oscillating local field potential of the intact PC network, the data from isolated PC neurons are consistent with the hypothesis that dopamine and serotonin modulate network dynamics, whereas glutamate is involved in generating the basic oscillation of local field potential in the PC. 6. The optical studies of fura-2-loaded cells showed that several treatments that increase the rate of action-potential production lead to elevations in intracellular calcium. Optical studies of intracellular calcium may be useful for multisite measurements of activity in the intact, oscillating PC lobe network.

Action Potentials↗

PubMed1992

Amino acids and serotonin in Limax maximum after a tryptophan devoid diet.

1. Animals avoid diets lacking an essential amino acid, such as tryptophan (TRP), the precursor for serotonin (5-HT). 5-HT is important in the control of feeding. 2. To study the effects of TRP deprivation, slugs were fed TRP-devoid (DEV) or control (COR) diets. 3. Food intake was depressed in DEV, as expected, but after 2 weeks, the serontonergic metacerebral giant cell in DEV was still functional. 4. Neither brain 5-HT nor plasma TRP concentration was affected. 5. Compared with food-restricted animals that had reductions in most amino acids, the DEV group sustained a marked plasma amino acid imbalance.

Amino Acids↗

PubMed1992

Odors can induce feeding motor responses in the terrestrial mollusc Limax maximus.

Highly developed odor learning was shown in the terrestrial slug Limax maximus. In addition, several key cellular elements of the neural network that controls ingestive feeding have been identified. The results of 3 experiments demonstrate an interaction between odor input and ingestive feeding in that olfactory stimulation with behaviorally attractive odors summed with tactile stimulation from plain agar to produce ingestion of plain agar. Agar ingestion did not occur in the absence of attractive odor stimulation. The adequacy of odor stimulation to trigger agar ingestion was altered by associative learning. Innately attractive odors rendered repellent by associative learning no longer triggered agar ingestion, whereas innately repellent odors rendered attractive by conditioning triggered agar ingestion. The newly discovered feeding command cells in the Limax cerebral ganglion are a logical cellular locus for this interaction.

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PubMed1991

Opiate agonists activate feeding in Limax: comparison of in vivo and in vitro effects.

The neural control system for feeding in the terrestrial mollusc Limax maximus is modulated by at least two major families of peptides. Sequence homology between one of the peptides known to modulate Limax feeding and some members of the opioid peptide family suggested that opioid peptides might also modulate Limax feeding. Experiments with the mu agonist morphine and the kappa agonist U50,488H showed that the probability of feeding, but not meal size, was increased by morphine injection into intact animals, whereas the length of feeding motor program responses elicited from the isolated lip-brain preparation of Limax was augmented by U50,488H. The behavioral effect of morphine was blocked by naltrexone injection, whereas the physiological effect of U50,488H was blocked by naloxone. Factors that influence the behavioral and electrophysiological effects of opioids on mollusc feeding are discussed.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1990

Odour-modulated collective network oscillations of olfactory interneurons in a terrestrial mollusc.

Determination of the dynamical structure of neural circuits--the general principles of how neural activity varies with time and manipulates information--is a prerequisite to understanding their computational function. Rhythmically active or oscillating neural circuits are particularly interesting dynamical structures, as rhythms and oscillations are a prominent feature of mammalian central nervous system electrophysiology. Coherent oscillations by networks of interneurons are observed in the vertebrate olfactory system and have recently been described in mammalian visual cortex. These interneuronal networks display oscillations in local field potential (LFP) and probability of producing action potentials that are highly correlated between subcircuits sharing the same stimulus features. Much less is known about the existence and importance of network oscillations in the higher centres of invertebrates. Here we report that a network of olfactory interneurons in the cerebral ganglion of the terrestrial mollusc Limax maximus also displays coherent oscillations in LFP which are modified by odour input. This dynamical structure could be central to the odour recognition and odour learning ability of Limax.

Action Potentials↗

PubMed1990

Analysis of associative learning in the terrestrial mollusc Limax maximus. II. Appetitive learning.

The odor and taste processing systems of the terrestrial mollusc Limax maximus have been shown capable of a number of complex computations. Most of the complex higher-order features of Limax learning have been demonstrated using differential aversive conditioning. The present experiments probe the appetitive learning ability of Limax. In the first experiment a differential appetitive classical conditioning procedure was used. An aversive CS+ odor was paired with an attractive taste while a CS- odor was explicitly unpaired with the attractive taste. This appetitive conditioning procedure dramatically increased the preference for the CS+ odor. Further experiments determined the time course of acquisition, the effect of an extinction procedure and long-term retention of the appetitive conditioning. Now that Limax has been shown capable of appetitive conditioning, the neural network simulation of Limax learning, called LIMAX, can be examined for its ability to display appetitive conditioning.

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PubMed1989

Serotonin-stimulated biochemical events in the procerebrum of Limax.

1. The procerebrum (PC) of the terrestrial slug Limax maximus is of interest as a potential site of olfactory information processing (Gelperin et al., 1989). The neuromodulator serotonin is present in the procerebrum and can elicit action potentials from cultured procerebral neurons. We have investigated the effects of serotonin on second-messenger signaling systems and protein phosphorylation as a prelude to studies on long-term synaptic plasticity in the Limax procerebral lobe. 2. We found that several biochemical changes are triggered within 20 min of adding serotonin to the isolated procerebral lobe: adenylate cyclase is activated, protein phosphorylation and synthesis are modulated, and phosphatidylinositol-metabolism is stimulated. 3. Serotonin causes a rapid synthesis of cAMP, reaching a 20- to 30-fold increase within 1 min. Serotonin affects the rate of phosphorylation of several proteins, detected after a brief (20-min) incubation of the procerebral lobe in [32P]phosphate-containing medium. The level of synthesis of several proteins is altered by serotonin, as determined by alterations in [35S]methionine incorporation during a 20-min incubation. Serotonin also causes a slow accumulation of inositoltrisphosphate. 4. Our study shows that within a short time (less than 20 min) serotonin can influence several second-messenger signaling systems and the functional state and abundance of proteins in the procerebral lobe. These serotonin-stimulated events should have direct consequences for intercellular communication in the odor-processing network of the procerebral lobe.

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PubMed1988

Distribution of FMRFamide-like immunoreactivity in the nervous system of the slug Limax maximus.

The distribution of FMRFamide-like immunoreactive neurons in the nervous system of the slug Limax maximus was studied using immunohistochemical methods. Approximately one thousand FMRFamide-like immunoreactive cell bodies were found in the central nervous system. Ranging between 15 micron and 200 micron in diameter, they were found in all 11 ganglia of the central nervous system. FMRFamide-like immunoreactive cell bodies were also found at peripheral locations on buccal nerve roots. FMRFamide-like immunoreactive nerve fibres were present in peripheral nerve roots and were distributed extensively throughout the neuropil and cell body regions of the central ganglia. They were also present in the connective tissue of the perineurium, forming an extensive network of varicose fibres. The large number, extensive distribution and great range in size of FMRFamide-like immunoreactive cell bodies and the wide distribution of immunoreactive fibres suggest that FMRFamide-like peptides might serve several different functions in the nervous system of the slug.

Animals↗

PubMed1988

Distribution of GABA-like immunoreactive neurons in the slug Limax maximus.

Immunohistochemical techniques were used to study the distribution of gamma-amino butyric acid (GABA)-like immunoreactive neurons in the nervous system of the slug Limax maximus. Approximately 170 GABA-like immunoreactive cell bodies were found in the central nervous system. These were located in the cerebral, buccal and pedal ganglia. Most GABA-like immunoreactive neurons had small cell bodies, which were aggregated into discrete clusters within the cerebral and pedal ganglia. Three pairs of longer, uniquely identifiable, GABA-like immunoreactive cells were found in the cerebral ganglion. GABA-like immunoreactive nerve fibres were also found in all of the central ganglia but were absent from peripheral nerves. These results suggest that GABA acts as a central neurotransmitter in the slug. The possible roles of GABA-ergic neurotransmission in the slug are discussed.

Animals↗

PubMed1987

Acetylcholine activates cerebral interneurons and feeding motor program in Limax maximus.

The cellular and network effects of acetylcholine (ACh) on the control system for feeding in Limax maximus were measured by intracellular recordings from feeding command-like interneurons and whole nerve recordings from buccal ganglion motor nerve roots that normally innervate the ingestive feeding muscles. The buccal ganglion motor nerve root discharge pattern that causes rhythmic feeding movements, termed the feeding motor program (FMP), was elicited either by attractive taste solutions applied to the lip chemoreceptors or by ACh applied to the cerebral ganglia. The ability of exogenous ACh applied to the cerebral ganglia to trigger FMP was blocked by the cholinergic antagonists curare and atropine. If the strength of the lip-applied taste stimulus was in the range of 1-2 times threshold, cerebral application of the cholinergic antagonists blocked or greatly decreased the ability of lip-applied taste solutions to trigger FMP (5 of 8 trials). The cerebral feeding interneurons, some of which activate FMP when stimulated intracellularly, are excited by small pulses of ACh applied directly to the cell body from an ACh-filled micropipette. A pulse of ACh that activates several of the feeding interneurons simultaneously triggers FMP. The data suggest that under certain stimulus conditions an obligatory set of cholinergic synapses onto the feedininterneurons must be activated for taste inputs to trigger ingestion. The determination of ACh's action within the feeding control system is necessary for understanding how enhanced cholinergic transmission leads to prolonged associative memory retention (Sahley, et al., 1986).

Acetylcholine↗

PubMed1987

Aminergic and peptidergic amplification of intracellular cyclic AMP levels in a molluscan neural network.

1. Serotonin (5-hydroxytryptamine; 5-HT), dopamine (DA), and small cardioactive peptide B (SCPB) can activate adenylate cyclase and increase the intracellular cyclic AMP (cAMP) levels in the Limax procerebrum (PC), with differing time courses and to differing extents. 5-HT and SCPB are potent stimulators of adenylate cyclase, and when both were applied simultaneously, an additive effect was observed. 2. In contrast, DA shows a great variability in the time course of cAMP synthesis and is a weak stimulator. Ergonovine, a DA antagonist, failed to inhibit cyclase activation, indicating that ergonovine-sensitive receptors are absent or ergonovine-sensitive DA receptors are not coupled to adenylate cyclase. 3. 5-HT and SCPB cause a rapid synthesis of cAMP, reaching the maximum 20- to 30-fold increase within a minute. DA's effect is slow in onset and very prolonged, reaching a maximum of only a two- to three-fold increase in the cAMP level. Reasons for variability in DA action are discussed.

Animals↗

PubMed1987

Localization and synthesis of monoamines in regions of Limax CNS controlling feeding behavior.

Localization and synthesis of dopamine and serotonin in the cerebral and buccal ganglia of Limax maximus were studied. A combination of fluorescence histochemistry, immunocytochemistry, and microchemical analysis showed that both amines were localized to particular cell groups and fiber tracts within and between the two sets of ganglia. Since these ganglia control feeding behavior, which is readily modified by associative learning, these studies have direct bearing on analysis of both motor control and learning mechanisms.

Animals↗

PubMed1986

Dietary choline augments associative memory function in Limax maximus.

Previous clinical and experimental work has shown that increased dietary intake of choline elevates blood choline and brain acetylcholine levels. This change in neuronal acetylcholine concentration may augment learning and memory functions. We tested this prediction using the mollusc Limax maximus, an animal which can be readily conditioned to avoid food odors. In our experiments, initial learning of a food avoidance task was not augmented by the high choline diet. However, the duration of memory retention was prolonged. In previous studies, we have shown that intake of the choline enriched diet significantly increases blood choline and amplifies transmission at an identified cholinergic synapse in Limax. Together, these results support the involvement of cholinergic synapses in the memory retention mechanism.

Animals↗

PubMed1986

Post-ingestive food-aversion learning to amino acid deficient diets by the terrestrial slug Limax maximus.

An agar-based artificial diet containing carbohydrates, fats and twenty amino acids was constructed. This diet is highly palatable and nutritionally complete for Limax maximus as demonstrated by significant ingestion on first encounter, consistent ingestion on subsequent days and good growth of young slugs fed this diet. Removing methionine, an essential amino acid, from the complete diet produces a food which is initially as palatable as the complete diet, but after one day's intake the amount of this deficient diet eaten is greatly reduced. Removing alanine, a nonessential amino acid, does not produce any decrement in feeding relative to the complete diet. A single meal can be sufficient for establishing the aversion to the deficient diet. Following seven days of feeding on the deficient diet the aversion is retained with little or no attenuation for at least 30 days and does not generalize to either a known 'safe' food or a novel food. Evidence of a mild neophobia towards the artificial diet which attenuated after one or two meals was seen. The learned aversion to the deficient diet is reversible if slugs are repeatedly fed the complete diet following feeding on the deficient diet. Also, slugs initially fed the complete diet will develop an aversion to the methionine-deficient diet after sampling it. Slugs readily ate the artificial diets when these were offered 7 days post-hatch. The methionine-deficient diet however was not eaten in large amounts after the first meals and did not support growth. Baby slugs fed the methionine-deficient diet for 10 days and then maintained on rat chow ate only small amounts when the deficient diet was presented again 126 days later, while baby slugs fed the complete diet or an alanine deficient diet for 10 days ate large amounts when these diets were presented 126 days later. Supplementing the methionine-deficient diet with an injection of methionine into the haemocoel one hour after the completion of a meal completely blocks the development of a learned aversion while injection of Limax saline does not. These results are best explained by the hypothesis that the slugs acquire, post-ingestively, an aversion to the taste and probably the odor of the diet as the result of associative learning.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

PubMed1984

In vitro expression of in vivo learning by an isolated molluscan CNS.

The associative learning functions of the central nervous system of Limax maximus have been established with behavioral experiments on intact animals (Sahley et al., J. comp. Physiol., 144 (1981) 1) and physiological experiments on the isolated CNS (Culligan and Gelperin, Brain Research, 266 (1983) 319). We now report experiments in which memory states were established by behavioral training and read out by a test procedure applied to the isolated brains derived from the trained animals. With a success rate of one-half we found that isolated lip-brain preparations derived from previously conditioned slugs express in vitro the learning acquired in vivo.

Animals↗

PubMed1984

Acetylcholine turnover in an autoactive molluscan neuron.

We have studied acetylcholine (ACh) turnover at the cholinergic synapse between an identified motoneuron, the salivary burster (SB), and the muscle cells of the salivary duct (SD) in the terrestrial mollusk Limax maximus. Electrophysiological recordings were made of the SB action potentials and the SB-elicited junction potentials (JPs) on the SD. The amplitude of the JP was used as a measure of ACh release by the SB. The SB is an autoactive neuron that discharges 1 to 12 bursts of action potentials per min. During sustained bursting activity, the SB is able to maintain transmitter release for 18 hr even in the absence of exogenous choline. The size of SB-elicited JPs does not vary during 18 hr of activity. If the choline uptake blocker, hemicholinium-3 (HC-3; 20 microM), is present in the saline, transmitter release and JP size are depressed by about 30% after 14 hr of activity. Thus, the SB is partially dependent upon choline reuptake for maintained ACh synthesis and release. In high (9.45 mM)-potassium (K+) saline, the SB fired tonically at twice its average spike frequency. JP amplitude initially increased, then declined to an amplitude which was 60% of the initial level. The addition of 20 microM HC-3 to the high-K+ saline caused a 75 to 100% decrease in JP size within 30 min. Thus, during high-frequency tonic firing, the SB was primarily dependent on choline reuptake for ACh synthesis and release. After JP size had been reduced in high-K+ saline containing HC-3, the SB-SD synapse was returned to normal choline-free saline. The SB resumed bursting activity. JP amplitude gradually increased over the next 30 min. Thus, high-frequency firing in HC-3 had not depleted the SB of its entire endogenous store of choline or ACh. If the synapse was fatigued in high-K+ saline containing HC-3 and then placed in saline enriched with 300 microM choline, JP size increased within minutes. Thus, uptake of choline for ACh synthesis and release may be a more rapid process than mobilization of an endogenous transmitter store. Finally, the SB-SD synapse was fatigued in high-K+ saline containing HC-3. HC-3 was then removed from the saline. The SB maintained high-frequency tonic activity. JP size did not increase unless choline was added to the saline.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMed1983

One-trial associative learning by an isolated molluscan CNS: use of different chemoreceptors for training and testing.

An isolated preparation of the lips, cerebral ganglia and buccal ganglia of the terrestrial slug, Limax maximus, can display one-trial associative learning. The lip-brain preparation can learn to suppress feeding motor program responses to lip stimulation with a standard food extract after a single pairing of food extract and quinidine stimulation to the isolated lips. Learning can occur with training stimuli applied to one lip and testing stimuli applied to the opposite, "naive' lip. Learning can also occur if the food extract and quinidine are applied during training to opposite lips. These results indicate that the synaptic alteration due to learning occurs in the CNS, not at the sensory periphery.

Animals↗