Alzheimer's disease, brain immune privilege and memory: a hypothesis.

The most distinctive feature of Alzheimer's disease (AD) is the specific degeneration of the neurons involved in memory consolidation, storage, and retrieval. Patients suffering from AD forget basic information about their past, loose linguistic and calculative abilities and communication skills. Thus, understanding the etiology of AD may provide insights into the mechanisms of memory and vice versa. The brain is an immunologically privileged site protected from the organism's immune reactions by the blood-brain barrier (BBB). All risk factors for AD (both cardiovascular and genetic) lead to destruction of the BBB. Evidence emerging from recent literature indicates that AD may have an autoimmune nature associated with BBB impairments. This hypothesis suggests that the process of memory consolidation involves the synthesis of novel macromolecules recognized by the immune system as "non-self" antigens. The objective of this paper is to stimulate new approaches to studies of neural mechanisms underpinning memory consolidation and its breakdown during AD. If the hypothesis on the autoimmune nature of AD is correct, the identification of the putative antigenic macromolecules might be critical to understanding the etiology and prevention of AD, as well as for elucidating cellular mechanisms of learning and memory.

Dual sensory-motor function for a molluskan statocyst network.

In mollusks, statocyst receptor cells (SRCs) interact with each other forming a neural network; their activity is determined by both the animal's orientation in the gravitational field and multimodal inputs. These two facts suggest that the function of the statocysts is not limited to sensing the animal's orientation. We studied the role of the statocysts in the organization of search motion during hunting behavior in the marine mollusk, Clione limacina. When hunting, Clione swims along a complex trajectory including numerous twists and turns confined within a definite space. Search-like behavior could be evoked pharmacologically by physostigmine; application of physostigmine to the isolated CNS produced "fictive search behavior" monitored by recordings from wing and tail nerves. Both in behavioral and in vitro experiments, we found that the statocysts are necessary for search behavior. The motor program typical of searching could not be produced after removing the statocysts. Simultaneous recordings from single SRCs and motor nerves showed that there was a correlation between the SRCs activity and search episodes. This correlation occurred even though the preparation was fixed and, therefore the sensory stimulus was constant. The excitation of individual SRCs could in some cases precede the beginning of search episodes. A biologically based model showed that, theoretically, the hunting search motor program could be generated by the statocyst receptor network due to its intrinsic dynamics. The results presented support for the idea that the statocysts are actively involved in the production of the motor program underlying search movements during hunting behavior.

Role of individual neurons and neural networks in cognitive functioning of the brain: a new insight.

The prevailing concept in modern neuroscience is that neuron networks play a dominant role in the functioning of the nervous system, whereas the role of individual neurons is rather insignificant. This concept suggests that "individuality" of single neurons is primarily determined by their place in a network rather than their intrinsic properties. Here I argue that individual neurons may play an important, if not decisive, role in performing cognitive functions of the brain. This tentative viewpoint is supported by experimental and clinical insights into disorders of cognitive functions and by genetic studies of cognitive abilities and disabilities. The results obtained in these studies indicate that many specific cognitive functions are carried out by groups of highly specialized neurons whose roles in performing these functions are genetically predetermined and their activity could not be substituted by the activity of other neurons. In this context, the main role of neural networks and intercellular interactions is to form dynamic ensembles of neurons involved in performing a given cognitive function.

Asymmetrical effect of GABA on the postural orientation in Clione.

The marine mollusk Clione limacina, when swimming, normally stabilizes the vertical body orientation by means of the gravitational tail reflexes. Horizontal swimming or swimming along inclined ascending trajectories is observed rarely. Here we report that GABA injection into intact Clione resulted in a change of the stabilized orientation and swimming with a tilt of approximately 45 degrees to the left. The analysis of modifications in the postural network underlying this effect was done with in vitro experiments. The CNS was isolated together with the statocysts. Spike discharges in the axons of two groups of motoneurons responsible for the left and right tail flexion, as well as in the axons of CPB3 interneurons mediating signals from the statocyst receptors to the motoneurons, were recorded extracellularly when the preparation was rotated in space. Normally the tail motoneurons of the left and right groups were activated with the contralateral tilt of the preparation. Under the effect of GABA, the gravitational responses in the right group of motoneurons and in the corresponding interneurons were dramatically reduced while the responses in the left group remained unchanged. The most likely site of the inhibitory GABA action is the interneurons mediating signals from the statocysts to the right group of tail motoneurons. The GABA-induced asymmetry of the left and right gravitational tail reflexes, observed in the in vitro experiments, is consistent with a change of the stabilized orientation caused by GABA in the intact Clione.

Neuronal mechanisms for the control of body orientation in clione II. Modifications in the activity of postural control system.

The marine mollusk Clione limacina, when swimming, can stabilize different body orientations in the gravitational field. The stabilization is based on the reflexes initiated by activation of the statocyst receptor cells and mediated by the cerebro-pedal interneurons that produce excitation of the motoneurons of the effector organs; tail and wings. Here we describe changes in the reflex pathways underlying different modes of postural activity; the maintenance of the head-up orientation at low temperature, the maintenance of the head-down orientation at higher temperature, and a complete inactivation of the postural mechanisms during defense reaction. Experiments were performed on the CNS-statocyst preparation. Spike discharges in the axons of different types of neurons were recorded extracellularly while the preparation was rotated in space through 360 degrees in different planes. We characterized the spatial zones of activity of the tail and wing motoneurons and the CPB3 interneurons mediating the effects of statocyst receptor cells on the tail motoneurons. This was done at different temperatures (10 and 20 degrees C). The "fictive" defense reaction was evoked by electrical stimulation of the head nerve. At 10 degrees C, a tilt of the preparation evoked activation in the tail motoneurons and wing retractor motoneurons contralateral to the tilt and in the wing locomotor motoneurons ipsilateral to the tilt. At 20 degrees C, the responses in the tail motoneurons and in the wing retractor motoneurons occurred reversed; these neurons were now activated with the ipsilateral tilt. In the wing locomotor motoneurons the responses at 20 degrees C were suppressed. During the defense reaction, gravitational responses in all neuron types were suppressed. Changes in the chains of tail reflexes most likely occurred at the level of connections from the statocyst receptor cells to the CPB3 interneurons. The changes in gravitational reflexes revealed in the present study are sufficient to explain the corresponding modifications of the postural behavior in Clione.

Neuronal mechanisms for the control of body orientation in Clione I. Spatial zones of activity of different neuron groups.

The marine mollusk Clione limacina, when swimming, can stabilize different body orientations in the gravitational field. Here we describe one of the modes of operation of the postural network in Clione-maintenance of the vertical, head-up orientation. Experiments were performed on the CNS-statocyst preparation. Spike discharges in the axons of different types of neurons were recorded extracellularly when the preparation was rotated in space through 360 degrees in different planes. We characterized the spatial zones of activity of the tail and wing motor neurons as well as of the CPB3 interneurons mediating the effects of statocyst receptor cells on the tail motor neurons. It was found that the activity of the tail motor neurons increased with deviation of the preparation from the normal, rostral-side-up orientation. Their zones of activity were very wide ( approximately 180 degrees ). According to the zone position, three distinct groups of tail motor neuron (T1-T3) could be distinguished. The T1 group had a center of the zone near the ventral-side-up orientation, whereas the zones of T2 and T3 had their centers near the left-side-up and the right-side-up positions, respectively. By comparing the zone of activity with the direction of tail bending elicited by each of the groups, one can conclude that gravitational reflexes mediated by the T1, T2, and T3 groups will evoke turning of the animal toward the head-up orientation. Two identified wing motor neurons, 1A and 2A, causing the wing beating, were involved in gravitational reactions. They were activated with the downward inclination of the ipsilateral side. Opposite reactions were observed in the motor neurons responsible for the wing retraction. A presumed motor effect of these reactions is an increase of oscillations in the wing that is directed downward and turning of Clione toward the head-up orientation. Among the CPB3 interneurons, at least four groups could be distinguished. In three of them (IN1, IN2, and IN3), the zones of activity were similar to those of the three groups (T1, T2, and T3) of the tail motor neurons. The group IN4 had the center of its zone in the dorsal-side-up position; a corresponding group was not found among the tail motor neurons. In lesion experiments, it was found that gravitational input mediated by a single CPB3 interneuron produced activation of its target tail motor neurons in their normal zones, but the strength of response was reduced considerably. This finding suggests that several interneurons with similar spatial zones converge on individual tail motor neurons. In conclusion, because of a novel method, activity of the neuronal network responsible for the postural control in Clione was characterized in the terms of gravitational responses in different neuron groups comprising the network.

Control of spatial orientation in a mollusc.

The main function of postural nervous mechanisms in different species, from mollusc to man, is to counteract the force of gravity and stabilize body orientation in space. Here we investigate the basic principles of postural control in a simple animal model, the marine mollusc Clione limacina. When swimming, C. limacina maintains its vertical orientation because of the activity of the postural neuronal network. Driven by gravity-sensing organs (statocysts), the network causes postural corrections by producing tail flexions. To understand how this function occurs, we studied network activity by using a new method. We used an in vitro preparation that consisted of the central nervous system isolated with the statocysts. Output signals from the network (electrical activity of tail motor neurons) controlled an electrical motor which rotated the preparation in space. We analysed the activity of individual neurons involved in postural stabilization under opened or closed feedback loop. When we closed this artificial feedback loop, the network stabilized the vertical orientation of the preparation. This stabilization is based on the tendency of the network to minimize the difference between the activities of the two antagonistic groups of neurons, which are driven by orientation-dependent sensory inputs.

Analysis of the central pattern generator for swimming in the mollusk Clione.

The pteropod mollusk Clione limacina swims by rhythmic movements of two wings. The central pattern generator (CPG) for swimming, located in the pedal ganglia, is formed by three groups of interneurons. The interneurons of the groups 7 and 8 are of crucial importance for rhythm generation. They are endogenous oscillators capable of generating rhythmic activity with a range of frequencies typical of swimming after extraction from the ganglia. This endogenous rhythmic activity is enhanced by serotonin. The interneurons 7 and 8 produce one prolonged action potential (about 100 ms in duration) per cycle. Prolonged action potentials contribute to determining the duration of the cycle phases. The interneurons of two groups inhibit one another determining their reciprocal activity. The putative transmitters of groups 7 and 8 interneurons are glutamate and acetylcholine, respectively. Transition from one phase to the other is facilitated by the plateau interneurons of group 12 that contribute to termination of one phase and to initiation of the next phase. Maintaining the rhythm generation and transition from one phase to the other is also promoted by postinhibitory rebound. The redundant organization of the swimming generator guarantees the high reliability of its operation. Generation of the swimming output persisted after the inhibitory input from interneurons 8 to 7 had been blocked by atropine. Activity of the swimming generator is controlled by a set of command neurons that activate, inhibit or modulate the operation of the swimming CPG in relation to a behaviorally relevant context.

Pattern generation.

Central pattern generators are neuronal ensembles capable of producing the basic spatiotemporal patterns underlying 'automatic' movements (e.g. locomotion, respiration, swallowing and defense reactions), in the absence of peripheral feedback. Different experimental approaches, from classical electrophysiological and pharmacological methods to molecular and genetic ones, have been used to understand the cellular and synaptic bases of central pattern generator organization and reconfiguration of generator operation in behaviorally relevant contexts. Recently, it has been shown that the high reliability and flexibility of central pattern generators is determined by their redundant organization. Everything that is crucial for generator operation is determined by a number of complementary mechanisms acting in concert; however, various mechanisms are weighted differently in determining different aspects of central pattern generator operation.

Control of locomotion in the marine mollusc Clione limacina. XI. Effects of serotonin.

The locomotor activity in the marine mollusc Clione limacina has been found to be strongly excited by serotonergic mechanisms. In the present study putative serotonergic cerebropedal neurons were recorded simultaneously with pedal locomotor motoneurons and interneurons. Stimulation of serotonergic neurons produced acceleration of the locomotor rhythm and strengthening of motoneuron discharges. These effects were accompanied by depolarization of motoneurons, while depolarization of the generator interneurons was considerably lower (if it occurred at all). Effects of serotonin application on isolated locomotor and non-locomotor pedal neurons were studied. Serotonin (5 x 10(-7) to 1 x 10(-6) M) affected most pedal neurons. All locomotor neurons were excited by serotonin. This suggests that serotonergic command neurons exert direct influence on locomotor neurons. Effects of serotonin on nonlocomotor neurons were diverse, most neurons being inhibited by serotonin. Some effects of serotonin on locomotor neurons could not be reproduced by neuron depolarization. This suggests that, along with depolarization, serotonin modulates voltage-sensitive membrane properties of the neurons. As a result, serotonin promotes the endogenous rhythmical activity in neurons of the C. limacina locomotor central pattern generator.

Control of locomotion in marine mollusk Clione limacina. VIII. Cerebropedal neurons.

1. The pteropod mollusk Clione limacina swims by rhythmical oscillations of two wings, and its spatial orientation during locomotion is determined by tail movements. The majority of neurons responsible for generation of the wing and tail movements are located in the pedal ganglia. On the other hand, the majority of sensory inputs that affect wing and tail movements project to the cerebral ganglia. The goal of the present study was to identify and characterize cerebropedal neurons involved in the control of the swimming central generator or motor neurons of wing and tail muscles. Cerebropedal neurons affecting locomotion-controlling mechanisms are located in the rostromedial (CPA neurons), caudomedial (CPB neurons), and central (CPC neurons) zones of the cerebral ganglia. According to their morphology and effects on pedal mechanisms, 10 groups of the cerebropedal neurons can be distinguished. 2. CPA1 neurons project through the ipsilateral cerebropedal connective to both pedal ganglia. Activation of a CPA1 by current injection resulted in speeding up of the locomotor rhythm and intensification of the firing of the locomotor motor neurons. 3. CPA2 neurons send numerous thin fibers into the ipsi- and contralateral pedal and pleural ganglia through the cerebropedal and cerebropleural connectives. They strongly inhibit the wing muscle motor neurons and, to a lesser extent, slow down the locomotor rhythm. 4. CPB1 neurons project through the contralateral cerebropedal connective to both pedal ganglia. They activate the locomotor generator. 5. CPB2 neurons also project, through the contralateral cerebropedal connective, to both pedal ganglia. They affect wing muscle motor neurons. 6. CPB3 neurons have diverse morphology: they project to the pedal ganglia either through the ipsilateral cerebropedal connective, or through the contralateral one, or through both of them. They affect putative motor neurons of the tail muscles. 7. CPC1, CPC2, and CPC3 neurons project through the ipsilateral cerebropedal connective to both pedal ganglia. They activate the locomotor generator. 8. CPC4 and CPC5 neurons project through the contralateral cerebropedal connective to the contralateral pedal ganglia. They activate the locomotor generator. 9. Serotonergic neurons were mapped in the CNS of Clione by immunohistochemical methods. Location and size of cells in two groups of serotonin-immunoreactive neurons in the cerebral ganglia appeared to be similar to those of CPA1 and CPB1 neurons. This finding suggests a possible mechanism for serotonin's ability to exert a strong excitatory action on the locomotor generator of Clione. 10. The role of different groups of cerebropedal neurons is discussed in relation to different forms of Clione's behavior in which locomotor activity is involved.

Control of locomotion in marine mollusk Clione Limacina. IX. Neuronal mechanisms of spatial orientation.

1. When swimming freely, the pteropod mollusk Clione limacina actively maintains a vertical orientation, with its head up. Any deflection from the vertical position causes a correcting motor response, i.e., bending of the tail in the opposite direction, and an additional activation of the locomotor system. Clione can stabilize not only the vertical orientation with its head up, but also the posture with its head down. The latter is observed at higher water temperature, as well as at a certain stage of hunting behavior. The postural control is absent in some forms of behavior (vertical migrations, defensive reactions, "looping" when hunting). The postural reflexes are driven by input from the statocysts. After removal of the statocysts, Clione was unable to maintain any definite spatial orientation. 2. Activity of the neuronal mechanisms controlling spatial orientation of Clione was studied in in vitro experiments, with the use of a preparation consisting of the CNS and statocysts. Natural stimulation (tilt of the preparation up to 90 degrees) was used to characterize responses in the statocyst receptor cells (SRCs). It was found that the SRCs depolarized and fired (10-20 Hz) when, during a tilt, they were in a position on the bottom part of the statocyst, under the statolith. Intracellular staining has shown that the SRC axons terminate in the medial area of the cerebral ganglia. Electrical connections have been found between some of the symmetrical SRCs of the left and right statocysts. 3. Gravistatic reflexes were studied by using both natural stimulation (tilt of the preparation) and electrical stimulation of SRCs. The reflex consisted of three components: 1) activation of the locomotor rhythm generator located in the pedal ganglia; this effect of SRCs is mediated by previously identified CPA1 and CPB1 interneurons that are located in the cerebral ganglia and send axons to the pedal ganglia; 2) bending the tail evoked by differential excitation and inhibition of different groups of tail muscle motor neurons; this effect is mediated by CPB3 interneurons; and 3) modification of wing movements by differential excitation and inhibition of different groups of wing motor neurons; this effect is mediated by CPB2 interneurons. 4. Gravistatic reflexes in the tail motor neurons were inhibited or reversed at a higher water temperature. 5. The SRCs are not "pure" gravitation sensory organs because they are subjected to strong influences from the CNS. In particular, CPC1 interneurons, participating in coordination of different aspects of the hunting behavior, exert an excitatory action on some of the SRCs, and inhibitory actions on others.(ABSTRACT TRUNCATED AT 400 WORDS)

Control of locomotion in marine mollusc Clione limacina. X. Effects of acetylcholine antagonists.

The swimming central pattern generator (CPG) of the pteropod mollusc Clione limacina is located in the pedal ganglia. It consists of three groups of interneurons (7, 8, and 12) which generate the rhythmical activity and determine the temporal pattern of the motor output, that is, phasic relations between different groups of motor neurons supplying dorsal (group 1 and 3 motor neurons) and ventral (group 2 and 4 motor neurons) muscles of the wings. In this work peripheral and central effects of acetylcholine (ACh) antagonists on the swimming control in C. limacina has been studied. The ACh antagonist atropine blocked transmission from the wing nerves to wing muscles, while gallamine triethiodide (Flaxedil), d-tubocurarine, and alpha-bungarotoxin did not affect the neuromuscular transmission. In the pedal ganglia, the ACh antagonists atropine and gallamine triethiodide blocked inhibitory postsynaptic potentials (IPSPs) produced by group 8 interneurons onto group 7 interneurons and motor neurons of groups 1 and 3. d-Tubocurarine and alpha-bungarotoxin did not affect IPSPs produced by group 8 interneurons. Although atropine and gallamine triethiodide blocked IPSPs produced by group 8 interneurons in antagonistic neurons, these drugs did not influence excitatory postsynaptic potentials (EPSPs) produced by group 8 interneurons onto group 12 interneurons. The main pattern of the swimming rhythm with an alternation of two phases of the swimming cycle persisted after elimination of inhibitory connections from group 8 interneurons to antagonistic neurons by the ACh antagonists. This suggests that there are redundant mechanisms in the system controlling C. limacina's swimming. This redundancy ensures reliable operation of the system and contributes to its flexibility.

Formation of connections between cultured identified neurones from the pleural ganglion of the pteropod mollusc Clione limacina.

A cluster of electrically interconnected neurosecretory cells (the 'white cells') involved in the control of reproductive behavior was identified in the right pleural ganglion of the marine mollusc, Clione limacina. Pleural ganglia also contain large neurons (PL1 and PL2) having no connections with each other and with the white cells. Most isolated white cells put into the simple unconditioned medium (50% L-15) adhered to the bottom of uncoated dishes and demonstrated neurite outgrowth for 7-10 days. If growing processes overlapped, the white cells formed electrical connections with each other, but they formed no connections with the PL1 and PL2 neurons. It is concluded that in the case which was under study cellular intrinsic properties were sufficient for the formation of 'correct' connections between neurones.

Statomotor system in the marine mollusk Clione limacina.

1. In the marine mollusk Clione limacina the "statomotor system" (named by analogy with the oculomotor system) has been found. This system includes a muscle that is directly attached to the statocysts connecting them with each other and with the inner surface of the body. 2. The statocyst muscle consists of four electrically coupled, mononuclear cells. Statocyst muscle cells do not generate spike-like potentials but only excitatory junctional potentials. 3. The motor input to the statocyst muscle correlates with the activity of the locomotor generator. This suggests that in the soft-bodied Clione contraction of the statocyst muscle stabilizes the statocysts into a standard "working" position in relation to coordinates of the body. This statocyst stabilization is important for Clione's spatial orientation during swimming.

Multiple effects of an identified proprioceptor upon gastric pattern generation in spiny lobsters.

1. Using deafferented preparations of the stomatogastric nervous system of spiny lobsters (Panulirus interruptus), we stimulated the central soma of the Anterior Gastric Receptor neuron (AGR) and analyzed sensorimotor integration in the gastric central pattern generator during rhythm production. 2. Driving AGR to spike tonically at lower frequencies (10-20/s) accelerated the gastric rhythm, while higher frequencies (> or = 30/s) suppressed it. 3. Shorter spike trains in AGR evoked phase-dependent resetting of the gastric rhythm. Repetitive trains could entrain rhythms to both longer and shorter cycle periods. Some pattern-generating effects are consistent with effects upon the lateral gastric neuron, an influential member of the gastric mill network. 4. AGR affected the burst intensity of many of the gastric neurons in specific, complex ways. Some power-stroke motor neurons were excited because AGR activated excitatory, premotor interneurons (E cells). However, AGR also activated parallel, seemingly inhibitory inputs, whose mechanism remains unclear. Still other effects on motor neurons may be mediated partly by synaptic interactions within the network.

Defense reaction in the pond snail Planorbis corneus. I. Activity of the shell-moving and respiratory systems.

1. In the intact pond snail Planorbis corneus, tactile or electrical stimulation of the skin evoked a biphasic general defense reaction. A weak stimulation evoked only the first phase of the reaction, represented as a fast pulling of the shell towards the head. With stronger stimulation, this phase was followed by the second phase that was comprised of three components: detachment from the substrate, slow retraction of the body into the shell, and letting out of air from the lung through the pneumostome. 2. About 70 motor neurons (MNs) of the columellar muscle have been revealed in different ganglia by means of their cobalt back-filling through the cut columellar nerve. A complicated pattern of electrical coupling was found for different groups of MNs. Excitation of individual MNs, evoked by current injection, resulted in contraction of the columellar muscle (CNS-columellar muscle preparation). The strongest contraction was evoked by the cerebral MNs; fast small contraction by the parietal MNs; and slow, long-latency contraction, by the pedal MNs. 3. In the same preparation, electrical stimulation of the cutaneous (lip) nerve evoked biphasic contraction of the columellar muscle (a first phase lasting approximately 3 s, and a second phase of up to 1 min). The temporal pattern of this response was similar to that of the defense reaction in the intact animal. A weak stimulation evoked only the first phases of the reaction, while a stronger stimulation evoked both phases. The amplitude of both the first and the second phase was graded with the strength of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Defense reaction in the pond snail Planorbis corneus. II. Central pattern generator.

1. In the isolated CNS of the pond snail Planorbis corneus, spontaneous bursts of activity in the motor neurons (MNs) supplying the columellar muscle were occasionally observed. The biphasic pattern of this activity, with a shorter (3-5 s) initial burst and longer (20-40 s) subsequent burst, was similar to that of the motor output during the general ("whole-body") defense reaction. In preparations consisting of the CNS isolated with the columellar muscle or with the lung, spontaneous biphasic contractions of the muscle as well as openings of the pneumostome with a temporal pattern characteristic of the defense reaction were observed. These findings demonstrated that the efferent pattern of the defense reaction in the snail is, to a large extent, produced by a special neuronal mechanism (the central pattern generator, CPG) triggered by the sensory input, rather than generated by ongoing processing of sensory input. The CPG consists of two components responsible for generation of two phases of the defense reaction. A characteristic feature of the CPG is that the magnitude of its response depends in a graded fashion on the strength of the initial stimulus. 2. In the pleural ganglia there are at least two electrically connected interneurons (DRN1s) that play an important role in generation of the first phase of the defense reaction. Processes of the DRN1s form a ring passing through all (except pedal and buccal) ganglia. The DRN1s received an excitatory input when a peripheral nerve was stimulated. They generated action potentials of long (0.2-2 s) duration. The DRN1 from the right ganglion was studied in more detail.(ABSTRACT TRUNCATED AT 250 WORDS)

Defense reaction in the pond snail Planorbis corneus. III. Response to input from statocysts.

1. In the intact pond snail Planorbis corneus, a rapid tilt in any plane evoked a defense reaction consisting of a fast movement of the shell towards the head, shortening of the foot, inhibition of locomotion and of rhythmical feeding movements. This reaction was similar to the first phase of the general defense reaction of Planorbis to cutaneous stimulation. 2. A method has been developed for inclination of the isolated CNS in space (up to 90 degrees) and simultaneous intracellular recordings from different neurons. 3. The statocyst receptor cells (SRCs) responded both phasically and tonically to the tilt. The SRCs differ in their spatial zones of sensitivity. 4. Essential manifestations of the defense reaction to the input from statocysts could be observed in the in vitro preparation of the CNS isolated with statocysts. Both tilting of the CNS and electrical stimulation of individual SRCs elicited an excitatory response in numerous neurons from different ganglia, including motor neurons (MNs) of the columellar muscle. This response was of "all-or-none" nature, and could be evoked by electrical stimulation of any SRC. The response was followed by a long (10-20 s) period of refractoriness. 5. Activation of SRCs resulted also in excitation of the giant dopaminergic cell in the left pedal ganglion (related to the control of respiration), in inhibition of the feeding rhythm generator, and in inhibition of the pedal neurons responsible for activation of the ciliary locomotor system. 6. Combined stimulation of two inputs able to evoke a defense reaction, i.e., those from the statocyst and from cutaneous nerve, revealed a strong interdependence of their central effects.(ABSTRACT TRUNCATED AT 250 WORDS)