Differential maintenance and frequency-dependent tuning of LTP at hippocampal synapses of specific strains of inbred mice.

Transgenic and knockout mice are used extensively to elucidate the molecular mechanisms of hippocampal synaptic plasticity. However, genetic and phenotypic variations between inbred mouse strains that are used to construct genetic models may confound the interpretation of cellular neurophysiological data derived from these models. Using in vitro slice stimulation and recording methods, we compared the membrane biophysical, cellular electrophysiological, and synaptoplastic properties of hippocampal CA1 neurons in four specific strains of inbred mice: C57BL/6J, CBA/J, DBA/2J, and 129/SvEms/J. Hippocampal long-term potentiation (LTP) induced by theta-pattern stimulation, and by repeated multi-burst 100-Hz stimulation at various interburst intervals, was better maintained in area CA1 of slices from BL/6J mice than in slices from CBA and DBA mice. At an interburst interval of 20 s, maintenance of LTP was impaired in CBA and DBA slices, as compared with BL/6J slices. When the interburst interval was reduced to 3 s, induction of LTP was significantly enhanced in129/SvEms slices, but not in DBA and CBA slices. Long-term depression (LTD) was not significantly different between slices from these four strains. For the four strains examined, CA1 pyramidal neurons showed no significant differences in spike-frequency accommodation, membrane input resistance, and number of spikes elicited by current injection. Synaptically-evoked glutamatergic postsynaptic currents did not significantly differ among CA1 pyramidal neurons in these four strains. Since the observed LTP deficits resembled those previously seen in transgenic mice with reduced hippocampal cAMP-dependent protein kinase (PKA) activity, we searched for possible strain-dependent differences in cAMP-dependent synaptic facilitation induced by forskolin (an activator of adenylate cyclase) and IBMX (a phosphodiesterase inhibitor). We found that forskolin/IBMX-induced synaptic facilitation was deficient in area CA1 of DBA/2J and CBA/J slices, but not in BL/6J and 129/SvEms/J slices. These defects in cAMP-induced synaptic facilitation may underlie the deficits in memory, observed in CBA/J and DBA/2J mice, that have been previously reported. We conclude that hippocampal LTP is influenced by genetic background and by the temporal characteristics of the stimulation protocol. The plasticity of hippocampal synapses in some inbred mouse strains may be "tuned" to particular temporal patterns of synaptic activity. From a broader perspective, our data support the notion that strain-dependent variation in genetic background is an important factor that can influence the synaptoplastic phenotypes observed in studies that use genetically modified mice to explore the molecular bases of synaptic plasticity.

The oculomotor system of decapod cephalopods: eye muscles, eye muscle nerves, and the oculomotor neurons in the central nervous system.

Fourteen extraocular eye muscles are described in the decapods Loligo and Sepioteuthis, and thirteen in Sepia; they are supplied by four eye muscle nerves. The main action of most of the muscles is a linear movement of the eyeball, only three muscles produce strong rotations. The arrangement, innervation and action of the decapod eye muscles are compared with those of the seven eye muscles and seven eye muscle nerves in Octopus. The extra muscles in decapods are attached to the anterior and superior faces of the eyes. At least, the anterior muscles, and presumably also the superior muscles, are concerned with convergent eye movements for binocular vision during fixation and capture of prey by the tentacles. The remaining muscles are rather similar in the two cephalopod groups. In decapods, the anterior muscles include conjunctive muscles; these cross the midline and each presumably moves both eyes at the same time during fixation. In the squids Loligo and Sepioteuthis there is an additional superior conjunctive muscle of perhaps similar function. Some of the anterior muscles are associated with a narrow moveable plate, the trochlear cartilage; it is attached to the eyeball by trochlear membranes. Centripetal cobalt fillings showed that all four eye muscle nerves have fibres that originate from somata in the ipsilateral anterior lateral pedal lobe, which is the oculomotor centre. The somata of the individual nerves show different but overlapping distributions. Bundles of small presumably afferent fibres were seen in two of the four nerves. They do not enter the anterior lateral pedal lobe but run to the ventral magnocellular lobe; some afferent fibres enter the brachio-palliovisceral connective and run perhaps as far as the palliovisceral lobe.

Light has many meanings for cephalopods.

The uses of light for cephalopods living at various depths are described. Aphakic apertures are shown in the eyes of Amphitretus and bolitaenids. In cirrate octopods, the eye is an open cup without lens and the retinal rhabdoms are disorganized. The photosensitive vesicles of cephalopods are extraocular receptors present either in the mantle or on the head. In some mesopelagic forms, they serve to compare the downwelling light with that emitted by the animal's own photophores, thus allowing regulation of counterillumination. In bathypelagic species, the photosensitive vesicles are very large and may serve to ensure reproduction at great depths. Some of the uses of the paired eyes in shallow water species are discussed. The mechanism for visual learning consists of a system for allowing many possible combinations of the output from numerous feature detectors. This begins with a set of columns in the optic lobes, followed by a tangential system. Outputs from the optic lobe lead to either attack or retreat: a third output leads to a memory system of four matrices allowing for interaction among the visual signals and between them and signals of taste or pain. These matrices allow conjunctive interaction between particular sets of signals and the setting up of memories ensuring appropriate responses. The matrices may be considered as analogous with those of the mammalian hippocampus. They include re-excitation among themselves and with the optic lobes. The tactile memory apparatus of the octopus has four similar lobes and also makes use of the four lobes of the visual system. These are therefore striking examples of adaptive networks allowing learned reactions by statistical selection among numerous channels. The anatomy, function, and generalizing powers of these networks emerged from Boycotts's early work, whose significance for computation can now be appreciated.

Computation in the Learning System of Cephalopods.

The memory mechanisms of cephalopods consist of a series of matrices of intersecting axes, which find associations between the signals of input events and their consequences. The tactile memory is distributed among eight such matrices, and there is also some suboesophageal learning capacity. The visual memory lies in the optic lobe and four matrices, with some re-exciting pathways. In both systems, damage to any part reduces proportionally the effectiveness of the whole memory. These matrices are somewhat like those in mammals, for instance those in the hippocampus. The first matrix in both visual and tactile systems receives signals of vision and taste, and its output serves to increase the tendency to attack or to take with the arms. The second matrix provides for the correlation of groups of signals on its neurons, which pass signals to the third matrix. Here large cells find clusters in the sets of signals. Their output re-excites those of the first lobe, unless pain occurs. In that case, this set of cells provides a record that ensures retreat. There is experimental evidence that these distributed memory systems allow for the identification of categories of visual and tactile inputs, for generalization, and for decision on appropriate behavior in the light of experience. The evidence suggests that learning in cephalopods is not localized to certain layers or "grandmother cells" but is distributed with high redundance in serial networks, with recurrent circuits.

The epistellar body and what followed from its discovery.

The sequence of discoveries that has followed the investigation of this small yellow spot shows the value of studies begun out of "mere curiosity". The spot occurs on the stellate ganglion of octopods. It proved to be an enclosed sac, perhaps a gland. The search for it in squids and cuttlefishes led to the discovery of the giant nerve fibres. At first they were thought to be veins but we soon showed that they were nerve fibres concerned with jet propulsion. Their action potentials, membranes and synapses have been used for thousand of studies, including those that led to the Hodkin Huxley equations. They have been the basis of much of modern neuroscience. The epistellar body itself proved not to be a gland but a photoreceptor. Comparable photosensitive vesicles are especially large in the heads of deep-sea squids. In the mesopelagic ones they allow the squid to conceal itself by counterillumination, matching its own light output to the light coming from above. In bathypelagic squids the vesicles are enormous and probably keep the animals in the dark, where they breed. The function of the epistellar body, lying within the mantle of octopods is still unknown. It may act in the transparent larval stage to trigger the ejection of luminous plankton, which would be a hazard.

Sympathetic innervation of the rectum and bladder of the skate and parallel effects of ATP and adrenalin.

1. Longitudinal muscles of the rectum of the skate are first briefly excited and then inhibited by stimulation of the sympathetic nerve fibres. 2. ATP, adrenalin and noradrenalin also produce inhibition. 3. 5HT is strongly excitatory but acetylcholine is only excitatory above 1 microM. 4. The rectum contracts strongly to mechanical stimulation; the response is not blocked by TTX. 5. The inhibitory actions of sympathetic stimulation or ATP were not blocked by guanethidine, propranalol, antazoline, theophylline or bee venom (apamin). 6. ATP continued to produce inhibition after the nerve response was blocked by TTX. 7. The urinary bladder gives slow rhythmic contractions, which are inhibited by nerve stimulation and by adrenalin but ATP has no action. 8. 5HT is strongly excitatory but acetylcholine has little action.

The effect of peptides on the motility of the stomach, intestine and rectum in the skate (Raja).

1. Pentagastrin (10(-8)-2 X 10(-6) M) was found to increase motor activity in the cardiac stomach and spiral intestine but only occasionally in the pyloric stomach and not at all in the rectum. 2. Substance P increased motor activity in both parts of the stomach and the rectum (10(-8)-5 X 10(-7) M) but had only a slight effect on the spiral intestine. 3. No effect on the activity of any part of the gut was seen with VIP (10(-7) M), neurotensin (2 X 10(-6) M) or bradykinin (2 X 10(-5) M). 4. The responses to pentagastrin or substance P were not abolished by TTX (10(-6) M). 5. The implications of these results for the understanding of the control of gut motility in elasmobranchs is discussed.

Short-lasting memory in lower nervous centers in Octopus.

Octopuses with the supraesophageal lobes split and the subesophageal centers isolated by cutting the cerebrobrachial connective on one or both sides were trained by food and shock rewards to discriminate between rough and smooth balls. Because there is a greater tendency to take the rough ball, training was done with the smooth ball positive for half the animals, and the rough ball positive for the others. In the animals with the cerebrobrachial connective cut only on one side, the subesophageal lobes showed no capacity to use the information gained by their opposite, intact, half-brains, which learned well. In animals with isolated subesophageal lobes, there was a decrease during each training session in the tendency to take both types of ball; however, this decrease did not persist from day to day. During each training session there were signs of discrimination between the balls by animals with isolated subesophageal lobes, but these also did not survive from day to day. In a series of training sessions spread over seven weeks, there was no change in results in animals with isolated subesophageal lobes when the smooth ball was positive. When the rough was positive the discrimination in its favor was slightly increased at later sessions.

The nervous system of Loligo. II. Suboesophageal centres.

A well-marked hierarchy of centres can be recognized within the suboesophageal lobes and ganglia of the arms. The inputs and outputs of each lobe are described. There are sets of motoneurons and intermediate motor centres, which can be activated either from the periphery or from above. They mostly do not send fibres up to the optic or higher motor centres. However, there is a large set of fibres running from the magnocellular lobe to all the basal supraoesophageal lobes. The centre for control of the four eye-muscle nerves in the anterior lateral pedal lobe receives many fibres direct from the statocyst and from the peduncle and basal lobes, but none direct from the optic lobe. The posterior lateral pedal is a backward continuation of the oculomotor centre, containing large cells that may be concerned in initiating attacks by the tentacles. An intermediate motor centre in the posterior pedal lobe probably controls steering. It sends fibres to the funned and head retractors, and by both direct and interrupted pathways to the fin lobe. It receives fibres from the crista nerve and basal lobes, but none direct from the optic lobe. The jet control centre of the ventral magnocellular lobe receives fibres from the statocyst and skin and also from the optic and basal lobes. Some of these last also give extensive branches throughout the palliovisceral lobes. The branching patterns of the dendritic collaterals differ in the various lobes. Some estimates are given of the numbers of synaptic points. The dendritic collaterals of the motoneurons spread through large volumes of neuropil and they overlap. The incoming fibres spread widely and each presumably activates many motoneurons either together or serially. Many of the lobes contain numerous microneurons with short trunks restricted to the lobe, but there are none of these cells in the chromatophore lobes or fin lobes. The microneurons have only few dendritic collaterals, in contrast to the numerous ones on the nearby motoneurons.