Nerve cell function and synaptic mechanisms

Nerve cells (neurones) are ‘excitable’ cells that can transduce a variety of stimuli into electrical signals, continuously sending information about the external and internal environment (in the form of sequences of action potentials) to the central nervous system (CNS). Interneurones in the CNS integrate this information and send signals along output (efferent) neurones to various parts of the body for the appropriate actions to be taken in response to environmental changes. Networks of neurones have been arbitrarily classified into various nervous systems that gather and transmit sensory information and control skeletal muscle function and autonomic function, etc. The junctions between neurones (synapses) are either electrical or chemical. The former permit the direct transfer of electrical current between cells, whereas the latter utilize chemical signalling molecules (neurotransmitters) to transfer information between cells. Neurotransmitters are mainly amino acids, amines or peptides (although other molecules such as purines and nitric oxide are utilized by some cells), and can be excitatory or inhibitory. Individual neurones within the CNS may receive synaptic inputs from thousands of other neurones. Therefore, each neurone ‘integrates’ this vast complexity of inputs and responds accordingly (either by remaining silent or firing action potentials to other neurones). Adaptations in the function and structure of chemical synapses in particular (synaptic plasticity) are thought to underlie the mechanisms mediating cognitive functions (learning and memory).     

Nerve cell function and synaptic mechanisms

Nerve cells (neurones) are ‘excitable’ cells that can transduce a variety of stimuli into electrical signals, continuously sending information about the external and internal environment (in the form of sequences of action potentials) to the central nervous system (CNS). Interneurones in the CNS integrate this information and send signals along output (efferent) neurones to various parts of the body for the appropriate actions to be taken in response to environmental changes. Networks of neurones have been arbitrarily classified into various nervous systems that gather and transmit sensory information and control skeletal muscle function and autonomic function, etc. The junctions between neurones (synapses) are either electrical or chemical. The former permit the direct transfer of electrical current between cells, whereas the latter utilize chemical signalling molecules (neurotransmitters) to transfer information between cells. Neurotransmitters are mainly amino acids, amines or peptides (although other molecules such as purines and nitric oxide are utilized by some cells), and can be excitatory or inhibitory. Individual neurones within the CNS may receive synaptic inputs from thousands of other neurones. Therefore, each neurone ‘integrates’ this vast complexity of inputs and responds accordingly (either by remaining silent or firing action potentials to other neurones). Adaptations in the function and structure of chemical synapses in particular (synaptic plasticity) are thought to underlie the mechanisms mediating cognitive functions (learning and memory).     

Nerve cell function and synaptic mechanisms

Nerve cells (neurones) are ‘excitable’ cells which can transduce a variety of stimuli into electrical signals, continuously sending information about the external and internal environment (in the form of sequences of action potentials) to the central nervous system (CNS). Interneurones in the CNS integrate this information and send signals along output (efferent) neurones to various parts of the body for the appropriate actions to be taken in response to environmental changes. Networks of neurones have been arbitrarily classified into various nervous systems which gather and transmit sensory information and control skeletal muscle function and autonomic function, etc. The junctions between neurones (synapses) are either electrical or chemical. The former permit the direct transfer of electrical current between cells, whereas the latter utilize chemical signalling molecules (neurotransmitters) to transfer information between cells. Neurotransmitters are mainly amino acids, amines or peptides (although other molecules such as purines and nitric oxide are utilized by some cells), and can be excitatory or inhibitory. Individual neurones within the CNS may receive synaptic inputs from thousands of other neurones. Therefore, each neurone ‘integrates’ this vast complexity of inputs and responds accordingly (either by remaining silent or firing action potentials to other neurones). Adaptations in the function and structure of chemical synapses in particular (synaptic plasticity) are thought to underlie the mechanisms mediating cognitive functions (learning and memory).     

Calcium and neuronal function

Calcium is unique among metals because its ions have a very large concentration gradient across the plasma membrane of all cells, from 10^–3 M Ca²⁺ outside, to 10^–7 M Ca²⁺ inside. This gradient is maintained by the use of metabolic energy through ion pumping, and its existence allows cells to use transient increases in the intracellular Ca²⁺ concentration as signals, which regulate cell function. In neurones these Ca signals are initiated by electrical activity (action potentials) which open voltage-dependent Ca channels in the plasma membrane, allowing Ca to enter the cell. Intracellular Ca signals can also be produced by transmitters at synapses, which open Ca channels, either directly, or indirectly by causing local depolarization and the opening of voltage-dependent Ca channels. The main effects of Ca signals on neurones are to alter their electrical activity, by modifying the opening and closing of Na and K channels, and to stimulate the release of transmitter substance. Ca has a host of other effects, such as the regulation of metabolic activity, the regulation of cell growth, and the long-term modification of synaptic efficiency, and it is even implicated in the destruction of neurones.     

Cannabinoid sensitivity and synaptic properties of 2 GABAergic networks in the neocortex

Distinct networks of gamma-aminobutyric acidergic interneurons connected by electrical synapses can promote different patterns of activity in the neocortex. Cannabinoids affect memory and cognition by powerfully modulating a subset of inhibitory synapses; however, very little is known about the synaptic properties of the cannabinoid receptor-expressing neurons (CB(1)-positive irregular spiking [CB(1)-IS]) in the neocortex. Using paired recordings in neocortical slices, we 1st report here that synapses of CB(1)-IS cells, but not synapses of fast-spiking (FS) cells, are suppressed by release of endocannabinoids from pyramidal neurons. CB(1)-IS synapses were characterized by a very high failure rate that contrasted with the high reliability of FS synapses. Furthermore, CB(1)-IS cells received excitatory inputs less frequently compared with FS cells and made significantly less frequent inhibitory contacts onto local pyramids. These distinct synaptic properties together with their characteristic irregular firing suggest that CB(1)-IS cells play different role in neocortical function than that of FS cells. Thus, whereas the synaptic properties of FS cells can allow them to impose high-frequency rhythmic oscillatory activity, those of CB(1)-IS cells may lead to disruption of fast rhythmic oscillations. Our results suggest that activity-dependent release of cannabinoids, by blocking CB(1)-IS synapses, may alter the role of inhibition in neocortical circuits.     

Intercellular communication

There are 3 modalities for intercellular communications: the chemical substances secreted by some cells are transported at distance where they act as signals on other cells; the surface molecules of a group of cells interact with the neighbouring cells; some special junctions or nexus provide direct relations between cells. In the first modality the chemical signals operate in 3 ways: a) many cells secrete one ore more chemical signals which act as local mediators (paracrine model); these mediators act immediately or are destroyed after they influence the neighbouring cells; b) some specialised cells--endocrine cells--secrete hormones, which are liberated in small amounts into the blood and exert their effects on some target cells, able to recognise and to respond to the hormonal signal; c) the neurones secrete chemical mediators--neurotransmitters, which act at the level of some special junctions--the chemical synapses. Most biologic phenomena are under the overlapping control of both systems--thus they are regarded as neuroendocrine system. The nervous cells transmit the informations much more rapidly than the endocrine cells. The chemical signals are various, as regarding the structure and function: they are large polypeptides, small polypeptides, glycoproteins, amino-acids, steroid molecules derived from cholesterol and fatty acids. The ability of the cells to respond to an extracellular signal molecule depends on the existence of some specific proteins, included in the plasma membrane, called receptors. The chemical signals influence the target cells both by altering the properties or the synthesis rate of their own proteins or by initiating the synthesis of new proteins. The chemical signals induce rapid and transient or slow- and long-lasting responses. All the neurotransmitters and the majority of hormones are water-soluble; the steroid and thyroid hormones are relatively water insoluble; the mechanisms of influencing the target cells are dependent of this feature: the water-soluble molecules do not pass through the target cell membrane, they bind to the surface specific receptor while the insoluble molecules cross the plasma membrane of the target cell and bind to the cytoplasmatic receptors. It results that the water-soluble molecules mediate short-time responses while those insoluble--long-lasting responses. As regarding the local chemical mediators they are secreted by mast cells or they are represented by the large category of prostaglandins. They produce a great diversity of biological effects, they are rapidly destroyed, and this way, they don't penetrate into the blood stream in significant amounts. The majority of the receptors from the surface of activated cells generate some intracellular signals both by altering the activity of some membrane enzyme (adenilate cyclase) with the accumulation of cyclic MPA and by modifying the permeability of some membrane channels(Ca2+ channels). The target cell exposed to a signal for a long period of time loose often the ability to respond to this signal. This process called desensibilization is reversible and is explained by endocytosis of surface receptors together with the ligand and by their lysosomal destruction, by the degradation of the receptor molecular conformation which becomes unable to bind the ligand or by the lack of activation of membrane enzymes or the channels. The gap or nexus junctions are composed by some proteic particles which form a hydrophilic channel to assure the communication between 2 neighbouring cells. These junctions allow some molecules (amino-acids, monosaccharides, cAMP, nucleotides) to pass from a cell to another one, facilitating the chemical and electrical coupling. These structures show a low electrical resistance, but they are dynamic, some junctions have the capacity to change from a low resistance to a high resistance state, isolating the cells from communicating with their neighbours. Oxygen deprivation, the increase of intracellul     

INHALATION ANAESTHETICS EXHIBIT PATHWAY-SPECIFIC AND DIFFERENTIAL ACTIONS ON HIPPOCAMPAL SYNAPTIC RESPONSES IN VITRO

The effects of halothane, isoflurane and enflurane were comparedon three CNS excitatory synaptic pathways in vitro, to determinewhether selective actions described in vivo result from differentialeffects on anatomically distinct cortical pathways and neuronepopulations. Halothane (0.25–1.25 vol%) depressed postsynapticexcitability of CA1 pyramidal neurones in response to activationof stratum radiatum synaptic inputs, and concentration-dependentexcitatory (0.25–1.25 vol%) and depressant (1.5–2.0vol%) actions were observed on dentate granule neurone excitabilityand perforant path evoked synaptic responses. In contrast, isofluraneincreased CA1 neurone excitability (0.25–0.75 vol%) andproduced postsynaptic depression of dentate neurones (0.5–4.0vol%). Enflurane also increased CA1 excitability (0.5–4.0vol%), but depressed synaptic responses at equivalent concentrations,and produced mixed excitatory (0.25–1.0 vol%) and depressant(1.0–4.0 vol%) effects on dentate synaptic responses.Differential actions were also observed for the three anaestheticson stratum oriens excitatory inputs to CA 1 neurones, and onantidromic responses. A good correlation (r = 0.992) existsbetween the membrane / buffer partition coefficients of theseanaesthetics and their half-maximal concentrations for depressionof synaptic responses; however, this correlation does not reflectthe different, anaesthetic-specific actions observed. The resultsindicate that inhalation anaesthetics act at multiple and selectivehydrophobic recognition sites which are heterogenously distributedon different synaptic pathways. ^* Present address: Department of Anesthesia, Stanford UniversitySchool of Medicine, Stanford, California, U.S.A.     

Attenuation of gap-junction-mediated signaling facilitated anesthetic effect of sevoflurane in the central nervous system of rats

Accumulating evidence suggests that reduction of intrinsic excitability or synaptic excitation and/or an enhancement of synaptic inhibition underlie the general anesthetic condition. Besides chemical synapse, neurons could communicate with each other by electrical coupling via gap-junctions. We hypothesized that inhibition of cell-to-cell signaling through gap-junction in the central nervous system (CNS) is involved in the anesthetic mechanism of volatile anesthetics. The minimum alveolar concentration (MAC) of sevoflurane was measured after the intracerebroventricular (ICV) or intrathecal (IT) administration of carbenoxolone (CBX), a gap-junction inhibitor, in vivo. The spontaneous oscillation in membrane currents of locus coeruleus neurons that results from electrical coupling between neurons was also recorded from young rat pontine slices by the patch clamp method, and the effect of sevoflurane on this oscillation was examined in vitro. The ICV administration of CBX (125 and 250 micro g/rat) significantly reduced the MAC of sevoflurane dose-dependently, whereas IT injection failed to inhibit the MAC. Sevoflurane at clinically relevant concentrations (0.1-0.5 mM) suppressed the spontaneous oscillation in membrane current concentration-dependently. These suppressions were significant at 0.5 mM with both amplitude and frequency. We suggest that suppression of gap-junction-mediated signaling in the CNS is involved in the anesthetic-induced immobilization by sevoflurane. IMPLICATIONS: The intracerebroventricular administration of the gap-junction inhibitor, carbenoxolone, reduced the MAC of sevoflurane, and sevoflurane suppressed the signaling through gap-junctions in the central nervous system. The inhibition of gap-junctions may be one of the mechanisms and the site of action of sevoflurane.     

Selective amplification of neocortical neuronal output by fast prepotentials in vivo

Neocortical cells integrate inputs from thousands of presynaptic neurons distributed along their dendritic arbors. Propagation of postsynaptic potentials to the soma is crucial in determining neuronal output. Using intracellular recordings in anesthetized and non-anesthetized, naturally awake and sleeping cats, we found evidence for generation of fast, all-or-none events recorded at the soma in about 20% of regular-spiking and intrinsically-bursting neurons. These events, termed fast prepotentials (FPPs), were suppressed by hyperpolarizing the neurons or by inhibiting synaptic transmission with perfusion of Ca2+-free artificial cerebrospinal fluid. FPPs could be evoked by activation of specific cortical inputs and allowed neurons to fire at more hyperpolarized levels of membrane potentials. Thus, FPPs represent a powerful mechanism to boost the output of neocortical neurons in response to given inputs. We further found evidence for modulation of FPPs generation across the waking-sleep cycle, indicating important changes in the integrative properties of neocortical neurons in different states of vigilance. We suggest that FPPs represent attenuated spikes generated in hot spots of the dendritic arbor and constitute a powerful mechanism to reinforce the functional connections between specific elements of the cortical networks.     

Functional maturation of excitatory synapses in layer 3 pyramidal neurons during postnatal development of the primate prefrontal cortex

In the primate dorsolateral prefrontal cortex (DLPFC), the density of excitatory synapses decreases by 40-50% during adolescence. Although such substantial circuit refinement might underlie the adolescence-related maturation of working memory performance, its functional significance remains poorly understood. The consequences of synaptic pruning may depend on the properties of the eliminated synapses. Are the synapses eliminated during adolescence functionally immature, as is the case during early brain development? Or do maturation-independent features tag synapses for pruning? We examined excitatory synaptic function in monkey DLPFC during postnatal development by studying properties that reflect synapse maturation in rat cortex. In 3-month-old (early postnatal) monkeys, excitatory inputs to layer 3 pyramidal neurons had immature properties, including higher release probability, lower alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-D-aspartate (NMDA) ratio, and longer duration of NMDA-mediated synaptic currents, associated with greater sensitivity to the NMDA receptor subunit B (NR2B) subunit-selective antagonist ifenprodil. In contrast, excitatory synaptic inputs in neurons from preadolescent (15 months old) and adult (42 or 84 months old) monkeys had similar functional properties. We therefore conclude that the contribution of functionally immature synapses decreases significantly before adolescence begins. Thus, remodeling of excitatory connectivity in the DLPFC during adolescence may occur in the absence of widespread maturational changes in synaptic strength.     

Summation of unitary IPSPs elicited by identified axo-axonic interneurons

We provided recent experimental evidence that coincident unitary events sum slightly sublinearly when targeting closely located postsynaptic sites. Simultaneous activation of many co-aligned inputs might lead to more significant nonlinear interactions especially in compartments of relatively small diameter. The axon initial segment of pyramidal cells has a limited volume and it receives inputs only from a moderate number of axo-axonic interneurons. We recorded the interaction of unitary axo-axonic inputs targeting a layer 4 pyramidal cell and determined the exact number and position of synapses mediating the effects. Both axo-axonic cells established three synaptic release sites on the axon initial segment of the postsynaptic cell which received a total of 19 synapses. The summation of identified inhibitory postsynaptic potentials (IPSPs) was slightly sublinear (9.4%) and the time course of sublinearity was slower than that of the IPSPs. Repeating the experiment while holding the postsynaptic cell in voltage clamp mode showed linear summation of inhibitory postsynaptic currents (IPSCs), suggesting that a local decrease in driving force could contribute to the sublinear summation measured in voltage recordings. The results indicate that moderate sublinearity during the interaction of neighboring inputs might be preserved in cellular compartments of relatively small volume, even if a considerable portion of all afferents converging to the same domain is simultaneously active.     

Effects of enflurane on gill withdrawal behaviors and the ability of gill motor neurones to elicit gill Contractions in Aplysia

We used the Aplysia gill withdrawal reflex model system in order to study how enflurane effected both gill withdrawal adaptive behaviors and the activity of single identified neurones which are involved with the mediation of the gill withdrawal response. We found that a continuous superfusion of enflurane (0.5 and 1.0%) solution over the abdominal ganglion (the CNS) resulted in an increase in the spontaneous gill respiratory movements; an increase in the spontaneous discharges in identified central motor neurones; and a depolarizing shift in the resting membrane potential of these neurones. Enflurane also significantly effected the ability of the gill motor neurones to elicit a gill contraction when the motor neurone was depolarized to produce action potentials by passing depolarizing current into the neurone. Although in most cases the ability of the motor neurone to elicit a gill withdrawal contraction was decreased, that in one third of the cases was increased. Enflurane may exert its actions by effecting the activity of CNS control neurones which exert both facilitatory and suppressive control over the peripheral nervous system in the gill as well as by having direct effects on the motor neurones.(Komatsu H, Lukowiak K, Ogli K: Effects of enflurane on gill withdrawal behaviors and the ability of gill motor neurones to elicit gill contractions in Aplysia. J Anesth 7: 434--441, 1993)     

How waves go down the bowel

Faradic stimulation of the small bowel of the rabbit causes a disturbance to spread out from 3 to 20 cm. orad and caudad. As a rule these wavelets travel slightly farther and faster caudad than orad and they almost always cause contraction of the muscle. There is rarely any sign of Bayliss' and Starling's law in the bowel of the rabbit.There is considerable evidence to show that conduction in the bowel takes place by way of neurones in Auerbach's plexus. The synapses between these neurones are probably valve-like and favor conduction in the caudad direction; they appear to be highly susceptible to anoxemia because in the rabbit peristaltic rushes disappear immediately after the death of the animal. They are susceptible also to the action of nicotine.The nerve cells are remarkably resistant to anoxemia as shown by the fact that in the cat they do not seem to lose their function when the circulation is shut off for five hours. Certain forms of paralytic ileus may perhaps be due to a blockage by toxins or by nervous inhibition of the synapses between the conducting neurones in Auerbach's plexus. Tonic contraction rings which sometimes produce intestinal obstruction may we11 be produced by a loss of function in another group of neurones which presumably are attached directly to the muscle.     

Formation et régénération synaptique

Synapse formation is probably the key process in neural development allowing signal transmission between nerve cells. As an interesting model of synapse maturation, we considered first the neuromuscular junction (NMJ), whose development is particularly dependent on intercellular interactions between the motor nerve and the skeletal muscle. Nerve and muscle have distinct roles in synaptic compartment differentiation. The initial steps of this differentiation and motor endplate formation require several postsynaptic molecular agents including agrin, the tyrosine kinase receptor MuSK and rapsyn. The agrin or motoneuron dependence of this process continues to be debated while the following steps of axonal growth and postsynaptic apparatus maintenance essentially depend on neuronal agrin and a neuron-specific signal dispersing ectopic AChR aggregate remainders, possibly mediated by acetylcholine itself. Neuregulin is essentially involved in Schwann's cell survival and guidance for axonal growth. In this paper, we will discuss the similarities between Central Nervous System (CNS) synaptic formation and Motor innervation. The limited ability of the CNS to create new synapses after nervous system injury will be then discussed with a final consideration of some new strategies elaborated to circumvent the limitations of lesion extension processes.     

骨骼对中枢神经系统调控作用的研究进展

骨骼一直被认为是惰性器官。近年来,研究发现骨骼作为一个重要的内分泌组织,通过感知和整合不同刺激,向中枢神经系统发送信号。骨骼影响中枢系统功能的机制,可能是通过分泌骨源性因子（骨钙素、骨硬化蛋白、Dickkopf相关蛋白1、脂质运载蛋白2、成纤维细胞生长因子23）,或者通过骨源性细胞（骨髓间充质干细胞、骨髓来源的小胶质样细胞）的生物调控。本文对以上骨骼影响中枢神经系统生物学作用的潜在机制进行初步探讨,为防治中枢神经系统疾病提供新方向。     

Synaptic and vascular associations of neurons containing cyclooxygenase-2 and nitric oxide synthase in rat somatosensory cortex

Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme for prostanoid synthesis that is present in cortical pyramidal neurons and highly implicated in control of cerebral blood flow during neural activity. We examined the electron microscopic localization of COX-2 and neuronal nitric oxide synthase (nNOS), a functionally related enzyme, in the somatosensory cortex of rat brain to determine the relevant functional sites. COX-2 immunoreactivity was detected in significantly more somatodendritic than axonal profiles, while nNOS was more often seen in axon terminals. The dendritic COX-2 was localized to endomembranes near synaptic inputs from axon terminals, some of which contained nNOS. Conversely, COX-2 terminals formed asymmetric, excitatory-type synapses with dendrites containing nNOS. The dendritic and axonal profiles containing COX-2 as well as those containing nNOS were minimally separated from penetrating arterioles and capillaries by filamentous glial processes. The perivascular COX-2 labeled terminals were among those that also formed axo-dendritic synapses, suggesting that the release of prostanoids and/or excitatory transmitters from a single terminal may simultaneously affect neuronal activity and cerebral blood flow. Thus, COX-2 has a compartmental distribution in somatosensory cortical neurons consistent with the local neuronal synthesis of prostanoids that are involved in neurovascular coupling and whose actions are modulated by nitric oxide.     

Entropy and cortical activity: information theory and PET findings.

Functional segregation requires convergence and divergence of neuroanatomical connections. Furthermore, the nature of functional segregation suggests that (1) signals in convergent afferents are correlated and (2) signals in divergent efferents are uncorrelated. The aim of this article is to show that this arrangement can be predicted mathematically, using information theory and an idealized model of cortical processing. In theory, the existence of bifurcating axons limits the number of independent output channels from any small cortical region, relative to the number of inputs. An information theoretic analysis of this special (high input:output ratio) constraint indicates that the maximal transfer of information between inputs, to a cortical region, and its outputs will occur when (1) extrinsic connectivity to the area is organized such that the entropy of neural activity in afferents is optimally low and (2) connectivity intrinsic to the region is arranged to maximize the entropy measured at the initial segments of projection neurons. Under the constraints of the model, a low entropy is synonymous with high correlations between axonal firing rates (and vice versa). Consequently this antisymmetric arrangement of functional activity in convergent and divergent connections underlying functional segregation is exactly that predicted by the principle of maximum preservation of information, considered in the context of axonal bifurcation. The hypothesis that firing in convergent afferents is correlated (has low entropy) and spatially coherent was tested using positron emission tomographic measurements of cortical synaptic function in man. This hypothesis was confirmed.     

Asymmetric synaptic depression in cortical networks

Synaptic depression is essential for controlling the balance between excitation and inhibition in cortical networks. Several studies have shown that the depression of intracortical synapses is asymmetric, that is, inhibitory synapses depress less than excitatory ones. Whether this asymmetry has any impact on cortical function is unknown. Here we show that the differential depression of intracortical synapses provides a mechanism through which the gain and sensitivity of cortical circuits shifts over time to improve stimulus coding. We examined the functional consequences of asymmetric synaptic depression by modeling recurrent interactions between orientation-selective neurons in primary visual cortex (V1) that adapt to feedforward inputs. We demonstrate analytically that despite the fact that excitatory synapses depress more than inhibitory synapses, excitatory responses are reduced less than inhibitory ones to increase the overall response gain. These changes play an active role in generating selective gain control in visual cortical circuits. Specifically, asymmetric synaptic depression regulates network selectivity by amplifying responses and sensitivity of V1 neurons to infrequent stimuli and attenuating responses and sensitivity to frequent stimuli, as is indeed observed experimentally.     

Heterogeneous Targets of Dopamine Synapses in Monkey Prefrontal Cortex Demonstrated by Serial Section Electron Microscopy: A Laminar Analysis Using the Silver-enhanced Diaminobenzidine Sulfide (SEDS) Immunolabeling Technique

Dopamine projections to the cerebral cortex have been implicatedin normal and pathological cognitive processes, notably, Parkinson'sdisease and schizophrenia. To help elucidate the function ofthese dopamine axons, they were characterized by serial sectionelectron microscopy in individual layers of monkey prefrontalcortex. Dopamine immunoreactivity was visualized with a silverprecipitation technique that allowed clear resolution of theinternal structures and cell membranes of labeled axons. Apartfrom the occasional large microtubule-filled axon, dopamineaxons were thin and varicose with many clear synaptic vesiclesand fewer densecore vesicles. With few exceptions, dopaminesynapses were symmetric and quite small, seen in only one tothree serial sections. A determination of the "synaptic incidence"showed that only 39% of labeled varicosities formed identifiablesynapses. However, it is certain that some small synapses couldnot be visualized even in serial sections, and it is possiblethat the vast majority if not all varicosities form synapses.Except for one soma, dendritic spines and shafts were the recipientsof dopamine synapses. Many postsynaptic shafts were small andspiny, indicating that they were distal pyramidal dendrites.However, some postsynaptic shafts especially in supragranularlayers had distinctly nonpyramidal features. These lacked spines,had a high density of synaptic inputs, and often had a strikinglyvaricose morphology. The data suggest that the majority of dopaminesynapses in all layers are on pyramidal cells, but that a significantfraction are on presumed GA-BAergic nonpyramidal cells.     

Learning-facilitated synaptic plasticity at CA3 mossy fiber and commissural-associational synapses reveals different roles in information processing

Subregion-dependent differences in the role of the hippocampus in information processing exist. Recently, it has emerged that a special relationship exists between the expression of persistent forms of synaptic plasticity in hippocampal subregions and the encoding of different types of spatial information. Little is known about this type of information processing at CA3 synapses. We report that in freely behaving rats, long-term potentiation (LTP) is facilitated at both mossy fiber (mf)-CA3 and commissural-associational (AC)-CA3 synapses by exploration of a novel (empty) environment. Exploration of large spatial landmarks facilitates long-term depression (LTD) at mf-CA3 synapses and impairs synaptic depression at AC-CA3 synapses. Novel exploration of small environmental features does not facilitate LTD at mf synapses but facilitates persistent LTD at AC synapses. Thus, depending on the quality of the information synaptic plasticity at AC-CA3 and mf-CA3 synapses is differentially modulated. These data suggest that expression of LTP as a result of environmental change is a common property of hippocampal synapses. However, LTD at mf synapses or AC synapses may subserve distinct and separate functions within the CA3 region.