RESUMEN
KEY POINTS: To understand how a network operates, its elements must be identified and characterized, and the interactions of the elements need to be studied in detail. In the present study, we describe quantitatively the connectivity of two classes of inhibitory neurons in the hippocampal CA3 area (parvalbumin-positive and cholecystokinin-positive interneurons), a key region for the generation of behaviourally relevant synchronous activity patterns. We describe how interactions among these inhibitory cells and their local excitatory target neurons evolve over the course of physiological and pathological activity patterns. The results of the present study enable the construction of precise neuronal network models that may help us understand how network dynamics is generated and how it can underlie information processing and pathological conditions in the brain. We show how inhibitory dynamics between parvalbumin-positive basket cells and pyramidal cells could contribute to sharp wave-ripple generation. ABSTRACT: Different hippocampal activity patterns are determined primarily by the interaction of excitatory cells and different types of interneurons. To understand the mechanisms underlying the generation of different network dynamics, the properties of synaptic transmission need to be uncovered. Perisomatic inhibition is critical for the generation of sharp wave-ripples, gamma oscillations and pathological epileptic activities. Therefore, we aimed to quantitatively and systematically characterize the temporal properties of the synaptic transmission between perisomatic inhibitory neurons and pyramidal cells in the CA3 area of mouse hippocampal slices, using action potential patterns recorded during physiological and pathological network states. Parvalbumin-positive (PV+) and cholecystokinin-positive (CCK+) interneurons showed distinct intrinsic physiological features. Interneurons of the same type formed reciprocally connected subnetworks, whereas the connectivity between interneuron classes was sparse. The characteristics of unitary interactions depended on the identity of both synaptic partners, whereas the short-term plasticity of synaptic transmission depended mainly on the presynaptic cell type. PV+ interneurons showed frequency-dependent depression, whereas more complex dynamics characterized the output of CCK+ interneurons. We quantitatively captured the dynamics of transmission at these different types of connection with simple mathematical models, and describe in detail the response to physiological and pathological discharge patterns. Our data suggest that the temporal propeties of PV+ interneuron transmission may contribute to sharp wave-ripple generation. These findings support the view that intrinsic and synaptic features of PV+ cells make them ideally suited for the generation of physiological network oscillations, whereas CCK+ cells implement a more subtle, graded control in the hippocampus.
Asunto(s)
Región CA3 Hipocampal/fisiología , Colecistoquinina/fisiología , Interneuronas/fisiología , Parvalbúminas/fisiología , Células Piramidales/citología , Células Piramidales/fisiología , Transmisión Sináptica/fisiología , Potenciales de Acción/fisiología , Animales , Colecistoquinina/genética , Femenino , Proteínas Fluorescentes Verdes/genética , Técnicas In Vitro , Potenciales Postsinápticos Inhibidores/fisiología , Proteínas Luminiscentes/genética , Masculino , Ratones Transgénicos , Modelos Neurológicos , Parvalbúminas/genética , Regiones Promotoras Genéticas , Proteína Fluorescente RojaAsunto(s)
Asma/rehabilitación , Climatoterapia , Dermatitis Atópica/terapia , Proteína Catiónica del Eosinófilo/metabolismo , Interleucina-16/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Adulto , Asma/sangre , Asma/fisiopatología , Pruebas de Provocación Bronquial , Quimiocina CCL17/inmunología , Quimiocina CCL17/metabolismo , Niño , Dermatitis Atópica/sangre , Dermatitis Atópica/fisiopatología , Proteína Catiónica del Eosinófilo/inmunología , Eosinófilos/metabolismo , Eosinófilos/patología , Prueba de Esfuerzo , Humanos , Inmunoglobulina E/sangre , Interleucina-16/inmunología , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Calidad de Vida , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Pruebas Cutáneas , Encuestas y CuestionariosRESUMEN
Endotoxins and allergens represent the major relevant contents of the atmospheric bioaerosol with regard to the triggering and exacerbation of allergic diseases. In this study, mattress concentrations of endotoxin and indoor allergens were measured in three hospitals in the alpine climate of Bavaria and in adjacent homes. Dust was collected from each of 10 mattresses according to a standardized protocol, and endotoxin was analyzed with the Limulus Amebocyte Lysate (LAL) test, indoor allergens Der p 1, Der f 1 and Fel d 1 were analyzed by ELISAs. The concentration of endotoxin in the mattresses did not differ significantly between different cities. The percentiles of endotoxin were significantly higher in hospitals than in homes. The concentrations of mite allergens (Der p 1 and Der f 1) in the dust were significantly lower in all hospitals than in homes. There was no significant difference of mite allergens between different time points. The concentrations of Fel d 1 were significantly higher in the autumn than in the summer (median: 1376 vs. 478ng/g). No significant differences of Fel d 1 were found between hospitals and homes or between different hospitals. As Fel d 1 concentrations reached levels at which cat allergic patients can experience symptoms, efforts had to be made to reduce the concentrations of Fel d 1 especially in hospitals. In contrast, mite allergens were low in hospitals, which can be clinically beneficial for patients with mite allergies.
Asunto(s)
Contaminación del Aire Interior/análisis , Alérgenos/análisis , Lechos , Endotoxinas/análisis , Exposición a Riesgos Ambientales/análisis , Animales , Antígenos Dermatofagoides/análisis , Lechos/microbiología , Gatos , Polvo/análisis , Ensayo de Inmunoadsorción Enzimática , Alemania , Glicoproteínas/análisis , Hospitales , Vivienda , Humanos , Ácaros/inmunología , Estadísticas no ParamétricasRESUMEN
In liver resection operations the Pringle (Baron) maneuver can be used for temporary ischemia by clamping the hepatoduodenal ligament intermittently. In this beagle canine model we investigated whether hemorheological parameters may alter in systemic, portal and hepatic venous blood and in arterial samples during-after Pringle maneuvers. In Pringle Group unilateral femoral artery and external jugular vein were cannulated. From median laparotomy the hepatoduodenal ligament was exposed. The portal venous system was catheterized via a mesenteric vein and through the inferior caval vein a catheter was led to the hepatic veins. After stabilization, a 15-minute Pringle maneuver was carried out three times with 5-minute interpolated reperfusion periods. In Control Group Pringle maneuvers were not made. Before and after Pringle maneuvers parallel blood samples were taken from the cannulated vessels for determining hematological parameters and erythrocyte aggregation. Following Pringle maneuvers erythrocyte deformability, blood and plasma viscosity were also tested. The results showed that besides systemic hemorheological effects of the intermittent Pringle maneuver local leukocyte count, hematocrit and erythrocyte aggregation index altered mainly in portal venous blood, depending on the repeating number of the maneuvers. Thus, investigations of hemorheological parameters might be useful to determine the optimal duration of the Pringle maneuver.
Asunto(s)
Agregación Eritrocitaria , Laparotomía/métodos , Hígado/cirugía , Modelos Biológicos , Animales , Perros , Humanos , Recuento de Leucocitos , Hígado/metabolismo , Masculino , Vena Porta/metabolismo , Vena Porta/cirugíaRESUMEN
Functionally distinct subsets of hippocampal inhibitory neurons exhibit large differences in the frequency, pattern and short-term plasticity of GABA release from their terminals. Heterogeneity is also evident in the ultrastructural features of GABAergic axon terminals examined in the electron microscope, but it is not known if or how this corresponds to interneuron subtypes. We investigated the feasibility of separating morphologically distinct clusters of terminal types, using the approach of measuring several ultrastructural parameters of GABAergic terminals in the CA1 area of the rat hippocampus. Septo-hippocampal axon terminals were anterogradely labeled by biotinylated dextran amine and visualized by pre-embedding immunogold staining to delineate one homogeneous terminal population. Long series (100-150) of ultrathin sections were cut from stratum oriens and stratum radiatum of the CA1 area, and GABAergic terminals were identified by post-embedding immunogold staining. Stereologically unbiased samples of the total GABAergic axon terminal population and a random sample of the septal axon terminals were reconstructed in 3D, and several of their parameters were measured (e.g. bouton volume, synapse surface, volume occupied by vesicles, mitochondria volume). Septal terminals demonstrated significantly larger mean values for most parameters than the total population of local GABAergic terminals. There was no significant difference between terminals reconstructed in the basal and apical dendritic regions of pyramidal cells, neither for the septal nor for the local population. Importantly, almost all parameters were highly correlated, precluding the possibility of clustering the local terminals into non-overlapping subsets. Factor and cluster analysis confirmed these findings. Our results suggest that similarly to excitatory terminals, inhibitory terminals follow an "ultrastructural size principle," and that the terminals of different interneuron subtypes cannot be distinguished by ultrastructure alone.
Asunto(s)
Hipocampo/fisiología , Hipocampo/ultraestructura , Terminales Presinápticos/fisiología , Terminales Presinápticos/ultraestructura , Ácido gamma-Aminobutírico/fisiología , Animales , Biotina/análogos & derivados , Dextranos , Colorantes Fluorescentes , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Masculino , Fibras Nerviosas/fisiología , Fibras Nerviosas/ultraestructura , Ratas , Ratas WistarRESUMEN
Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) catalyse the hydrolysis of the endocannabinoids anandamide and 2-arachidonoyl glycerol. We investigated their ultrastructural distribution in brain areas where the localization and effects of cannabinoid receptor activation are known. In the hippocampus, FAAH was present in somata and dendrites of principal cells, but not in interneurons. It was located mostly on the membrane surface of intracellular organelles known to store Ca(2+) (e.g. mitochondria, smooth endoplasmic reticulum), less frequently on the somatic or dendritic plasma membrane. MGL immunoreactivity was found in axon terminals of granule cells, CA3 pyramidal cells and some interneurons. In the cerebellum, Purkinje cells and their dendrites are intensively immunoreactive for FAAH, together with a sparse axon plexus at the border of the Purkinje cell/granule cell layers. Immunostaining for MGL was complementary, the axons in the molecular layer were intensively labelled leaving the Purkinje cell dendrites blank. FAAH distribution in the amygdala was similar to that of the CB(1) cannabinoid receptor: evident signal in neuronal somata and proximal dendrites in the basolateral nucleus, and hardly any labelling in the central nucleus. MGL staining was restricted to axons in the neuropil, with similar relative signal intensities seen for FAAH in different nuclei. Thus, FAAH is primarily a postsynaptic enzyme, whereas MGL is presynaptic. FAAH is associated with membranes of cytoplasmic organelles. The differential compartmentalization of the two enzymes suggests that anandamide and 2-AG signalling may subserve functional roles that are spatially segregated at least at the stage of metabolism.
Asunto(s)
Amidohidrolasas/metabolismo , Amígdala del Cerebelo/enzimología , Cerebelo/enzimología , Hipocampo/enzimología , Monoacilglicerol Lipasas/metabolismo , Terminales Presinápticos/enzimología , Sinapsis/enzimología , Amidohidrolasas/genética , Amígdala del Cerebelo/ultraestructura , Animales , Calbindina 2 , Calbindinas , Cerebelo/ultraestructura , Colecistoquinina/metabolismo , Técnica del Anticuerpo Fluorescente/métodos , Glutamato Descarboxilasa/metabolismo , Hipocampo/ultraestructura , Isoenzimas/metabolismo , Masculino , Ratones , Ratones Noqueados , Microscopía Inmunoelectrónica/métodos , Parvalbúminas/metabolismo , Ratas , Ratas Wistar , Proteína G de Unión al Calcio S100/metabolismo , Sinapsis/ultraestructuraRESUMEN
OBJECTIVE: Physical activity is an important and frequent trigger of airways obstruction in asthmatic children. We aimed to compare the efficacies of 50 microg salmeterol twice daily and 2 mg SCG four times daily with respect to protection from exercise induced bronchoconstriction (EIB). METHODS: Twenty seven children and adolescents aged 4 to 16 years with mild or moderate exercise induced asthma (FEV1 70% to 90% predicted) were admitted to the study. Exercise challenge was performed on a treadmill using a predefined protocol in order to produce 10 minutes of exercise at near-maximum targets. The trial had a randomised, cross-over design comprising a 3-day run-in period and two 7-day treatment periods, separated by a one-week washout period. RESULTS: The mean protective efficacy of salmeterol was larger than that of SCG. A difference between treatments of 39.7% (95% CI, - 0,8 to 68.9%) in favour of salmeterol was calculated using a Hodges-Lehmann-estimate. The maximum post-challenge fall in FEV subset 1 was significantly lower (p<0.001) after salmeterol than after SCG (- 5.6 +/- 6.4% vs. -12.1 +/- 9.3%, respectively). In addition, salmeterol improved base-line lung function to a greater degree than SCG. FEV1 increased by 0.4 l/sec after salmeterol, whereas no improvement was observed after SCG. CONCLUSIONS: A one-week treatment with salmeterol 50 microg b.i.d in asthmatic children and adolescents provided better protection against EIB and improved baseline lung function as compared to SCG four times daily.
Asunto(s)
Albuterol/análogos & derivados , Albuterol/farmacología , Antiasmáticos/farmacología , Asma Inducida por Ejercicio/prevención & control , Broncodilatadores/farmacología , Cromolin Sódico/farmacología , Adolescente , Albuterol/efectos adversos , Albuterol/uso terapéutico , Antiasmáticos/efectos adversos , Antiasmáticos/uso terapéutico , Asma Inducida por Ejercicio/tratamiento farmacológico , Asma Inducida por Ejercicio/fisiopatología , Broncodilatadores/efectos adversos , Broncodilatadores/uso terapéutico , Niño , Preescolar , Cromolin Sódico/efectos adversos , Cromolin Sódico/uso terapéutico , Estudios Cruzados , Ejercicio Físico/fisiología , Femenino , Humanos , Pulmón/efectos de los fármacos , Pulmón/fisiología , Pulmón/fisiopatología , Masculino , Xinafoato de SalmeterolRESUMEN
A subset of GABAergic neurons projecting to the medial septum has long been described in the hippocampus. However, the lack of information about their local connectivity pattern or their correspondence with any of the well-established hippocampal interneuron types has hampered the understanding of their functional role. Retrograde tracing combined with immunostaining for neurochemical markers in the adult rat hippocampus showed that nearly all hippocampo-septal (HS) neurons express somatostatin (>95%) and, in the hilus and CA3 stratum lucidum, many contain calretinin (>45%). In contrast, in stratum oriens of the CA1 and CA3 subfields, the majority of HS neurons contain somatostatin (>86%) and calbindin (>73%), but not calretinin. Because somatostatin-positive hippocampal interneurons have been most extensively characterized in the stratum oriens of CA1, we focused our further analysis on HS cells found in this region. In 18-20-day-old rats, intracellularly filled CA1-HS cells had extensive local axon collaterals crossing subfield boundaries and innervating the CA3 region and the dentate gyrus. Electron microscopic analysis provided evidence that the axon terminals of CA1-HS cells form symmetrical synapses selectively on GABAergic interneurons, both locally and in the CA3 region. In addition, double retrograde labelling experiments revealed that many CA1-HS neurons of the dorsal hippocampus also have collateral projections to the ventral hippocampus. Thus, CA1-HS cells innervate inhibitory interneurons locally and in remote hippocampal regions, in addition to targeting mostly GABAergic neurons in the medial septum. This dual projection with striking target selectivity for GABAergic neurons may be ideally suited to synchronize neuronal activity along the septo-hippocampal axis.
Asunto(s)
Hipocampo/fisiología , Interneuronas/fisiología , Inhibición Neural/fisiología , Núcleos Septales/fisiología , Animales , Hipocampo/ultraestructura , Interneuronas/ultraestructura , Masculino , Vías Nerviosas/fisiología , Vías Nerviosas/ultraestructura , Ratas , Ratas Wistar , Núcleos Septales/ultraestructuraRESUMEN
To elucidate the role of dendritic morphology in signal transfer, the passive propagation of somatic and dendritic potentials was compared in multi-compartment models of three interneuron subpopulations in the CA1 region. Nine calbindin-, 15 calretinin- and 10 parvalbumin-containing cells were modelled incorporating the detailed geometry, the currents of the action potentials in the soma, and the AMPA, N-methyl-D-aspartate and GABA-B receptor-mediated postsynaptic currents in the dendrites. The cable properties show characteristic differences among the subpopulations. The morphotonic length of calbindin and calretinin cell dendrites is larger than of parvalbumin cells. Thus parvalbumin cells are more compact than calbindin or calretinin cells unless the ratio of their axial and membrane resistivities exceeds the ratios of the other two cell types by more than 33%. In calbindin cells, the distal parts of the extremely long dendrites that invade the alveus are virtually isolated from the soma for passively propagating signals. The synaptic potentials evoked at a given morphotonic distance from the soma show larger differences locally on the dendrites than on the soma in all subpopulations. Both the somatic and dendritic amplitude ratios are the smallest in PV cells. In calbindin cells the somatic amplitude of synaptic potentials evoked at the same morphotonic distance from the soma is similar regardless of the number of branchpoints along their path. In calretinin and parvalbumin cells, from dendrites with long primary segments synaptic potentials reach the soma with larger amplitude than from dendrites that are branching close to the soma. The dendrites with the larger impact on somatic membrane potential are usually the dendrites that enter the stratum lacunosum-moleculare. These results indicate that dendritic morphology plays a role in changing the effectiveness of synaptic potentials evoked at different dendritic locations, and in this way is likely to be an important factor in determining the integrative properties of the different neuron populations.
Asunto(s)
Compartimento Celular/fisiología , Tamaño de la Célula/fisiología , Dendritas/metabolismo , Hipocampo/metabolismo , Interneuronas/metabolismo , Modelos Neurológicos , Transmisión Sináptica/fisiología , Animales , Proteínas de Unión al Calcio/metabolismo , Membrana Celular/metabolismo , Membrana Celular/ultraestructura , Dendritas/ultraestructura , Hipocampo/citología , Humanos , Interneuronas/citología , Red Nerviosa/citología , Red Nerviosa/metabolismo , Conducción Nerviosa/fisiología , Receptores de GABA-B/metabolismo , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transducción de Señal/fisiologíaRESUMEN
Immunocytochemical visualization of the neuron-specific K+/Cl- cotransporter, KCC2, at the cellular and subcellular level revealed an area- and layer-specific diffuse labelling, and a discrete staining outlining the somata and dendrites of some interneurons in all areas of the rat hippocampus. KCC2 was highly expressed in parvalbumin-containing interneurons, as well as in subsets of calbindin, calretinin and metabotropic glutamate receptor 1a-immunoreactive interneurons. During the first 2 postnatal weeks, an increase of KCC2 staining was observed in the molecular layer of the dentate gyrus, correlating temporally with the arrival of entorhinal cortical inputs. Subcellular localization demonstrated KCC2 in the plasma membranes. Immunoreactivity in principal cells was responsible for the diffuse staining found in the neuropil. In these cells, KCC2 was detected primarily in dendritic spine heads, at the origin of spines and, at a much lower level on the somata and dendritic shafts. KCC2 expression was considerably higher in the somata and dendrites of interneurons, most notably of parvalbumin-containing cells, as well as in the thorny excrescences of CA3 pyramidal cells and in the spines of spiny hilar and stratum lucidum interneurons. The data indicate that KCC2 is highly expressed in the vicinity of excitatory inputs in the hippocampus, perhaps in close association with extrasynaptic GABAA receptors. A high level of excitation is known to lead to a simultaneous net influx of Na+ and Cl-, as evidenced by dendritic swelling. KCC2 located in the same microenvironment may provide a Cl- extrusion mechanism to deal with both ion and water homeostasis in addition to its role in setting the driving force of Cl- currents involved in fast postsynaptic inhibition.
Asunto(s)
Proteínas Portadoras/metabolismo , Cloruros/metabolismo , Potenciales Postsinápticos Excitadores/fisiología , Hipocampo/metabolismo , Neuronas/metabolismo , Potasio/metabolismo , Simportadores , Sinapsis/metabolismo , Animales , Animales Recién Nacidos , Calbindina 2 , Calbindinas , Canales de Cloruro/metabolismo , Dendritas/metabolismo , Dendritas/ultraestructura , Giro Dentado/crecimiento & desarrollo , Giro Dentado/metabolismo , Giro Dentado/ultraestructura , Hipocampo/crecimiento & desarrollo , Hipocampo/ultraestructura , Inmunohistoquímica , Interneuronas/metabolismo , Interneuronas/ultraestructura , Masculino , Potenciales de la Membrana/fisiología , Microscopía Electrónica , Neuronas/ultraestructura , Parvalbúminas/metabolismo , Células Piramidales/metabolismo , Células Piramidales/ultraestructura , Ratas , Ratas Wistar , Receptores de Glutamato Metabotrópico/metabolismo , Proteína G de Unión al Calcio S100/metabolismo , Sinapsis/ultraestructura , Cotransportadores de K ClRESUMEN
The integrative properties of neurons depend strongly on the number, proportions and distribution of excitatory and inhibitory synaptic inputs they receive. In this study the three-dimensional geometry of dendritic trees and the density of symmetrical and asymmetrical synapses on different cellular compartments of rat hippocampal CA1 area pyramidal cells was measured to calculate the total number and distribution of excitatory and inhibitory inputs on a single cell.A single pyramidal cell has approximately 12,000 microm dendrites and receives around 30,000 excitatory and 1700 inhibitory inputs, of which 40 % are concentrated in the perisomatic region and 20 % on dendrites in the stratum lacunosum-moleculare. The pre- and post-synaptic features suggest that CA1 pyramidal cell dendrites are heterogeneous. Strata radiatum and oriens dendrites are similar and differ from stratum lacunosum-moleculare dendrites. Proximal apical and basal strata radiatum and oriens dendrites are spine-free or sparsely spiny. Distal strata radiatum and oriens dendrites (forming 68.5 % of the pyramidal cells' dendritic tree) are densely spiny; their excitatory inputs terminate exclusively on dendritic spines, while inhibitory inputs target only dendritic shafts. The proportion of inhibitory inputs on distal spiny strata radiatum and oriens dendrites is low ( approximately 3 %). In contrast, proximal dendritic segments receive mostly (70-100 %) inhibitory inputs. Only inhibitory inputs innervate the somata (77-103 per cell) and axon initial segments. Dendrites in the stratum lacunosum-moleculare possess moderate to small amounts of spines. Excitatory synapses on stratum lacunosum-moleculare dendrites are larger than the synapses in other layers, are frequently perforated ( approximately 40 %) and can be located on dendritic shafts. Inhibitory inputs, whose percentage is relatively high ( approximately 14-17 %), also terminate on dendritic spines. Our results indicate that: (i) the highly convergent excitation arriving onto the distal dendrites of pyramidal cells is primarily controlled by proximally located inhibition; (ii) the organization of excitatory and inhibitory inputs in layers receiving Schaffer collateral input (radiatum/oriens) versus perforant path input (lacunosum-moleculare) is significantly different.
Asunto(s)
Hipocampo/citología , Células Piramidales/ultraestructura , Sinapsis/fisiología , Sinapsis/ultraestructura , Animales , Dendritas/fisiología , Dendritas/ultraestructura , Hipocampo/fisiología , Hipocampo/ultraestructura , Masculino , Microscopía Electrónica , Microscopía Inmunoelectrónica , Células Piramidales/fisiología , Ratas , Ratas Wistar , Ácido gamma-Aminobutírico/análisisRESUMEN
The least known aspect of the functional architecture of hippocampal microcircuits is the quantitative distribution of synaptic inputs of identified cell classes. The complete dendritic trees of functionally distinct interneuron types containing parvalbumin (PV), calbindin D(28k) (CB), or calretinin (CR) were reconstructed at the light microscopic level to describe their geometry, total length, and laminar distribution. Serial electron microscopic reconstruction and postembedding GABA immunostaining was then used to determine the density of GABA-negative asymmetrical (excitatory) and GABA-positive symmetrical (inhibitory) synaptic inputs on their dendrites, somata, and axon initial segments. The total convergence and the distribution of excitatory and inhibitory inputs were then calculated using the light and electron microscopic data sets. The three populations showed characteristic differences in dendritic morphology and in the density and distribution of afferent synapses. PV cells possessed the most extensive dendritic tree (4300 microm) and the thickest dendrites. CR cells had the smallest dendritic tree (2500 microm) and the thinnest shafts. The density of inputs as well as the total number of excitatory plus inhibitory synapses was several times higher on PV cells (on average, 16,294) than on CB (3839) or CR (2186) cells. The ratio of GABAergic inputs was significantly higher on CB (29.4%) and CR (20.71%) cells than on PV cells (6.4%). The density of inhibitory terminals was higher in the perisomatic region than on the distal dendrites. These anatomical data are essential to understand the distinct behavior and role of these interneuron types during hippocampal activity patterns and represent fundamental information for modeling studies.
Asunto(s)
Hipocampo/citología , Interneuronas/citología , Proteínas del Tejido Nervioso/análisis , Sinapsis/fisiología , Sinapsis/ultraestructura , Vías Aferentes , Animales , Axones/fisiología , Axones/ultraestructura , Calbindina 2 , Calbindinas , Dendritas/fisiología , Dendritas/ultraestructura , Hipocampo/fisiología , Procesamiento de Imagen Asistido por Computador , Interneuronas/fisiología , Masculino , Parvalbúminas/análisis , Ratas , Ratas Wistar , Proteína G de Unión al Calcio S100/análisis , Ácido gamma-Aminobutírico/análisisRESUMEN
Ascending subcortical pathways effectively modulate hippocampal information processing. Two components, the cholinergic and serotonergic pathways have been demonstrated to play an important role in the generation of behaviour-dependent hippocampal EEG patterns. Several findings suggest that the above projections influence the activity of hippocampal interneurons. Here we review the available data from physiological, pharmacological and receptor localization experiments, drawing attention to the crucial role of interneurons in the transfer and amplification of subcortical effects on cortical information processing. We hypothesize that, by exerting diverse actions on different subsets of interneurons, the cholinergic and serotonergic systems might change the balance of somatic and dendritic inhibition, and consequently change the integrative properties of hippocampal principal cells.
Asunto(s)
Colina/fisiología , Hipocampo/fisiología , Neuronas/fisiología , Serotonina/fisiología , Ácido gamma-Aminobutírico/fisiología , Animales , Humanos , Interneuronas/fisiología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiologíaRESUMEN
Hippocampal inhibitory cells are diverse. It is supposed that they fall into functionally distinct subsets defined by a similar morphology and physiology. Switching between functions could be accomplished by activating receptors for modulating transmitters expressed selectively by different subsets of interneurons. We tested this hypothesis by comparing morphology, physiology, and neurotransmitter receptor expression for CA1 hippocampal interneurons. We distinguished 16 distinct morphological phenotypes and 3 different modes of discharge. Subsets of inhibitory cells were excited or inhibited by agonists at receptors for noradrenaline, muscarine, serotonin, and mGluRs. Most cells responded to 2 or 3 agonists, and 25 different response combinations were detected. Subsets defined by morphology, physiology, and receptor expression did not coincide, suggesting that hippocampal interneurons cannot easily be segregated into a few well-defined groups.
Asunto(s)
Hipocampo/citología , Hipocampo/fisiología , Interneuronas/fisiología , Inhibición Neural/fisiología , 2-Amino-5-fosfonovalerato/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Axones/fisiología , Tamaño de la Célula/fisiología , Cicloleucina/análogos & derivados , Cicloleucina/farmacología , Dendritas/fisiología , Antagonistas de Aminoácidos Excitadores/farmacología , Interneuronas/química , Interneuronas/ultraestructura , Muscarina/farmacología , Agonistas Muscarínicos/farmacología , Fármacos Neuroprotectores/farmacología , Neurotransmisores/fisiología , Norepinefrina/farmacología , Ratas , Receptores de Glutamato Metabotrópico/agonistas , Serotonina/farmacología , Simpatomiméticos/farmacología , Tetrodotoxina/farmacologíaRESUMEN
Neurons of a distinct type in CA1 area stratum radiatum of the rat hippocampus have been found to express a direct cellular form of long-term potentiation (LTP, Maccaferri & McBain, 1996, J. Neurosci. 16, 5334), but their functional identity, i.e. whether interneuron or principal cell, remained unknown. Whole cell recording from hippocampal slices in vitro was combined with light and electron microscopy to answer this question. LTP was robustly induced by a pairing protocol and physiological properties were measured in radiatum giant cells (RGCs) using biocytin containing pipettes. Reconstruction of the cells' dendritic and axonal arbor revealed morphological properties similar to CA1 pyramidal cells with some characteristic differences. They typically had two large diameter apical dendrites, or when only one dendrite arose, it soon bifurcated. Apical dendrites formed a dendritic tuft in stratum lacunosum-moleculare and the dendrites, but not the somata, were densely covered with conventional spines. The axon arose from the basal pole of the soma, descended to stratum oriens and emitted several axon terminals bearing collaterals that travelled horizontally, remaining in stratum oriens. The main, myelinated axon trunks turned towards the fimbria. In the electron microscope axon terminals were found to form asymmetrical synapses on postsynaptic dendritic shafts and dendritic spines in stratum oriens. The dendrites received asymmetrical synapses, mostly on their spines. The axon initial segments also received several synapses, a feature never observed on interneurons. All the above characteristics support the conclusion that RGCs are excitatory principal neurons.
Asunto(s)
Hipocampo/anatomía & histología , Hipocampo/citología , Interneuronas/clasificación , Interneuronas/citología , Células Piramidales/citología , Animales , Axones/fisiología , Axones/ultraestructura , Tamaño de la Célula/fisiología , Dendritas/fisiología , Dendritas/ultraestructura , Electrofisiología , Interneuronas/ultraestructura , Potenciación a Largo Plazo/fisiología , Células Piramidales/fisiología , Células Piramidales/ultraestructura , Ratas , Ratas Sprague-Dawley , Sinapsis/fisiología , Sinapsis/ultraestructuraRESUMEN
Hippocampal GABAergic interneurons are responsible for controlling the output and efficacy of synaptic input of large principal cell populations and, thereby, determine the oscillatory discharge patterns and synaptic plasticity in the hippocampus. Single interneurons are able to prevent repetitive firing of postsynaptic pyramidal cells (R. Miles, K. Tóth, A.I. Gulyás, N. Hájos, and T.F. Freund. Neuron, 16: 815-823, 1996), whereas on occasion a single pyramidal cell may be able to activate an interneuron under in vitro conditions (A.I. Gulyás, R. Miles, A. Sik, K. Tóth, N. Tamamaki, and T.F. Freund. Nature (London), 366: 683-687, 1993). Inhibition is therefore extremely powerful. Transient suppression of interneuronal activity allows the precise timing and synchronization of inhibitory postsynaptic potentials arriving at principal cells. A rhythmic suppression or modulation of interneuron discharge may be brought about by input from at least two major sources: (i) from other local interneurons or (ii) from subcortical centers. Of the possible local sources, in the present review particular attention will be paid to GABAergic neurons specialized to innervate other interneurons. Subcortical pathways known to modulate specific inhibitory functions in the hippocampus, i.e., the GABAergic and cholinergic septohippocampal and the serotonergic raphe hippocampal pathways, will also be reviewed. Roles of these control mechanisms may include the generation of theta and higher frequency oscillations and the selective removal of inhibition from the termination zone of specific excitatory afferents, thereby increasing their efficacy and (or) plasticity.
Asunto(s)
Hipocampo/citología , Interneuronas/fisiología , Acetilcolina/fisiología , Hipocampo/ultraestructura , Interneuronas/ultraestructura , Plasticidad Neuronal/fisiología , Neuronas Aferentes/fisiología , Células Piramidales/fisiología , Serotonina/fisiologíaRESUMEN
A specific antiserum against substance P receptor (SPR) labels nonprincipal neurons in the cerebral cortex of the rat (T. Kaneko et al. [1994], Neuroscience 60:199-211; Y. Nakaya et al. [1994], J. Comp. Neurol. 347:249-274). In the present study, we aimed to identify the types of SPR-immunoreactive neurons in the hippocampus according to their content of neurochemical markers, which label interneuron populations with distinct termination patterns. Markers for perisomatic inhibitory cells, parvalbumin and cholecystokinin (CCK), colocalized with SPR in pyramidallike basket cells in the dentate gyrus and in large multipolar or bitufted cells within all hippocampal subfields respectively. A dense meshwork of SPR-immunoreactive spiny dendrites in the hilus and stratum lucidum of the CA3 region belonged largely to inhibitory cells terminating in the distal dendritic region of granule cells, as indicated by the somatostatin and neuropeptide Y (NPY) content. In addition, SPR and NPY were colocalized in numerous multipolar interneurons with dendrites branching close to the soma. Twenty-five percent of the SPR-immunoreactive cells overlapped with calretinin-positive neurons in all hippocampal subfields, showing that interneurons specialized to contact other gamma-aminobutyric acid-ergic cells may also contain SPR. On the basis of the known termination pattern of the colocalized markers, we conclude that SPR-positive interneurons are functionally heterogeneous and participate in different inhibitory processes: (1) perisomatic inhibition of principal cells (CCK-containing cells, and parvalbumin-positive cells in the dentate gyrus), (2) feedback dendritic inhibition in the entorhinal termination zone (somatostatin and NPY-containing cells), and (3) innervation of other interneurons (calretinin-containing cells).
Asunto(s)
Hipocampo/fisiología , Neuronas/fisiología , Receptores de Neuroquinina-1/metabolismo , Ácido gamma-Aminobutírico/fisiología , Animales , Dendritas/metabolismo , Dendritas/ultraestructura , Giro Dentado/citología , Giro Dentado/fisiología , Giro Dentado/ultraestructura , Hipocampo/citología , Hipocampo/ultraestructura , Inmunohistoquímica , Interneuronas/fisiología , Interneuronas/ultraestructura , Masculino , Microscopía Electrónica , Terminales Presinápticos/fisiología , Terminales Presinápticos/ultraestructura , Células Piramidales/fisiología , Células Piramidales/ultraestructura , Ratas , Ratas WistarRESUMEN
Spine-free calretinin-immunoreactive (CR-IR) interneurons form a subpopulation of GABAergic cells in the rat hippocampus. A characteristic feature of these cells--located in all areas and layers--is the frequent dendro-dendritic and axo-dendritic contacts they form with each other. In this study we examined in detail the connectivity of these neurons by reconstructing their dendritic and axonal arbor and by identifying their postsynaptic targets. Radially running dendrites of CR-IR cells, located in different layers, intermingled into long braids. An average cell was in contact with dendrites of three to seven other CR-IR cells. Reconstruction of the dendritic trees from six consecutive sections demonstrated that at least 15 cells may participate in a dendro-dendritically connected cluster. Electron microscopical examination revealed that regularly spaced zonula adherentia connect the touching dendrites. The postsynaptic targets of CR-IR neurons have been examined using postembedding immunogold staining for GABA. CR-containing GABA-immunoreactive axons of local origin formed multiple symmetrical synaptic contacts (two to five) exclusively on GABAergic dendrites (CR-negative as well as CR-positive). Two to 10 CR-IR axons may converge onto a single CR-IR neuron, often from cells belonging to the same dendro-dendritically connected cluster. Using double immunocytochemistry, CR-IR cells were shown to heavily innervate calbindin D28k-containing interneurons and VIP-containing basket cells but avoided the parvalbumin-containing basket and axo-axonic cells. The unique connectivity of CR-IR cells may enable them to play a crucial role in the generation of synchronous, rhythmic hippocampal activity by controlling other interneurons terminating on different dendritic and somatic compartments of principal cells.
Asunto(s)
Hipocampo/anatomía & histología , Interneuronas/fisiología , Animales , Axones/ultraestructura , Calbindina 2 , Hipocampo/ultraestructura , Inmunohistoquímica , Interneuronas/ultraestructura , Masculino , Microscopía Electrónica , Ratas , Ratas Wistar , Proteína G de Unión al Calcio S100/análisis , Ácido gamma-Aminobutírico/análisisRESUMEN
Hippocampal synaptic inhibition is mediated by distinct groups of inhibitory cells. Some contact pyramidal cells perisomatically, while others terminate exclusively on their dendrites. We examined perisomatic and dendritic inhibition by recording from CA3 inhibitory and pyramidal cells and injecting biocytin to visualize both cells in light and electron microscopy. Single perisomatic inhibitory cells made 2-6 terminals clustered around the soma and proximal pyramidal cell processes. Dendritic cells established 5-17 terminals, usually on different dendrites of a pyramidal cells. Perisomatic terminals were larger than those facing dendritic membrane. Perisomatic inhibitory cells initiated the majority of simultaneous IPSPs seen in nearby pyramidal cells. Single IPSPs initiated by perisomatic sodium-dependent action potentials. Activation of inhibitory fibers terminating on dendrites could suppress calcium-dependent spikes. Thus, distinct inhibitory cells may differentially control dendritic electrogenesis and axonal output of hippocampal pyramidal cells.
Asunto(s)
Comunicación Celular , Dendritas/fisiología , Hipocampo/fisiología , Células Piramidales/fisiología , Potenciales de Acción/efectos de los fármacos , Animales , Axones/fisiología , Axones/ultraestructura , Calcio/farmacología , Electrodos , Cobayas , Hipocampo/ultraestructura , Técnicas In Vitro , Lisina/análogos & derivados , Microscopía Electrónica , Sodio/farmacología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The axonal arborization and postsynaptic targets of calbindin D28k (CB)-immunoreactive nonprincipal neurons have been studied in the rat dorsal hippocampus. Two types of neurons were distinguished on the basis of soma location, the characteristics of the dendritic free, and the axon arborisation pattern. Type I cells were located in stratum radiatum of the CA1 and CA3 regions and occasionally in strata pyramidale and oriens. These cells had multipolar or bitufted dendritic trees primarily located in stratum radiatum. Their axons could be followed for a considerable distance, arborised within stratum radiatum, and were covered with regularly spaced small boutons. As demonstrated with postembedding immunogold staining, their axon terminals were gamma-aminobutyric acid (GABA) immunoreactive, and formed symmetrical synapses predominantly on proximal and distal dendrites of pyramidal cells (28% and 58%, respectively), and occasionally on spines (9%) or on GABA-positive dendrites (5%). Type II cells were found exclusively in stratum oriens of the CA1 and CA3 regions and possessed large, fusiform cell bodies and long, horizontally oriented dendrites. Their axon initial segments turned towards the alveus and disappeared in a myelin sheet, which was often possible to follow into the white matter. We conclude that type I CB-immunoreactive cells are likely to represent a major source of inhibitory synapses in the dendritic region of pyramidal cells, which are responsible for the control of dendritic electrogenesis. The distribution of local collaterals of type II cells-if they have any-remains unknown, but their main axon is likely to project to the medial septum.