In the primate neocortex, little is known about the possible associations between functional subclasses of GABA neurons, their morphological properties and calcium-binding protein (CaBP) content. We ...used whole-cell current clamp recordings, combined with intracellular labeling and fluorescence immunohistochemistry, to determine these relationships for interneurons in layers 2–3 of monkey prefrontal cortex (PFC). Eighty-one interneurons were included in the analysis. Thirty-eight of these cells showed immunoreactivity for one of the three CaBPs tested. Co-localization of more than one CaBP was not observed in any of the interneurons examined. Interneurons with different CaBPs formed distinct populations with specific physiological membrane properties and morphological features. Parvalbumin (PV)-positive cells had the physiological properties characteristic of fast-spiking interneurons (FS) and the morphology of basket or chandelier neurons. Most calretinin (CR)-containing cells had the physiological properties ascribed to non-fast-spiking cells (non-FS) and a vertically oriented axonal morphology, similar to that of double bouquet cells. Calbindin (CB)-positive interneurons also had non-FS properties and included cells with double bouquet morphology or with a characteristic dense web of axonal collaterals in layer 1. Classification of the interneurons based on cluster analysis of multiple electrophysiological properties suggested the existence of at least two distinct groups of interneurons. The first group contained mainly PV-positive FS cells and the second group consisted predominantly of CR- and CB-positive non-FS interneurons. These findings may help to illuminate the functional roles of different groups of interneurons in primate PFC circuitry.
Departments of 1 Psychiatry and 2 Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania
Submitted 24 March 2008;
accepted in final form 14 July 2008
Differences in the developmental origin ...and relative proportions of biochemically distinct classes of cortical neurons have been found between rodents and primates. In addition, species differences in the properties of certain cell types, such as neurogliaform cells, have also been reported. Consequently, in this study we compared the anatomical and physiological properties of parvalbumin (PV)-positive basket interneurons in the prefrontal cortex of macaque monkeys and rats. The somal size, total dendritic length, and horizontal and vertical spans of the axonal arbor were similar in monkeys and rats. Physiologically, PV basket cells could be identified as fast-spiking interneurons in both species, based on their short spike and high-frequency firing without adaptation. However, important interspecies differences in the intrinsic physiological properties were found. In monkeys, basket cells had a higher input resistance and a lower firing threshold, and they generated more spikes at near-threshold current intensities than those in rats. Thus monkey basket cells appeared to be more excitable. In addition, rat basket cells consistently fired the first spike with a substantial delay and generated spike trains interrupted by quiescent periods more often than monkey basket cells. The frequency of miniature excitatory postsynaptic potentials in basket cells was considerably higher in rats than that in monkeys. These differences between rats and monkeys in the electrophysiological properties of PV-positive basket cells may contribute to the differential patterns of neuronal activation observed in rats and monkeys performing working-memory tasks.
Address for reprint requests and other correspondence: N. V. Povysheva, University of Pittsburgh School of Arts and Sciences, Department of Neuroscience, Langley A210, Pittsburgh, PA 15260 (E-mail: nvp1{at}pitt.edu )
In the prefrontal cortex (PFC) during working memory tasks fast-spiking (FS) interneurons might shape the spatial selectivity of pyramidal cell firing. In order to provide time control of pyramidal ...cell activity, incoming excitatory inputs should excite FS interneurons more vigorously than pyramidal cells. This can be achieved if subthreshold excitatory responses of interneurons are considerably stronger and faster than those in pyramidal neurons. Here we compared the functional properties of excitatory post-synaptic potentials (EPSPs) between pyramidal cells and FS interneurons in slices from monkey dorsolateral PFC and rat prelimbic cortex. Miniature, unitary (in connected pairs or by minimal stimulation) and compound (evoked by electrical stimulation of the white matter) EPSPs were recorded in whole cell mode. We found that EPSPs were significantly larger and faster in FS interneurons than those recorded from pyramidal cells, consistent with the idea of more efficient recruitment of FS interneurons compared to pyramidal neurons. Similar results were obtained in monkey and rat PFC, suggesting a stable role of FS interneurons in this circuitry across species.
•In the ventral horn (VH) chondroitin sulfate proteoglycan 4 (CSPG4) was associated with the surface of glial fibrillary acidic protein (GFAP)-positive processes of astrocytes located near the ...synapses.•In the region remote from the primary spinal cord lesion site, lectican expression was progressively reduced in perineuronal nets and perisynaptic extracellular matrix.•The proximity of GFAP-positive astrocytic processes to the neuronal perikaryon affects lectican, CSPG4, and glutamate transporter 1 surface expression in the VH region remote from the primary lesion site in the spinal cord.•After spinal cord injury there was an increase in the small guanosine triphosphatase cdc42 that resembled the dynamics of the increase in CSPG4.
Spinal cord injury (SCI) results in pronounced focal tissue damage with subsequent formation of a glial scar that blocks axon regeneration and regrowth. Cellular changes and the composition of the extracellular matrix in regions distal from the injured area remain poorly characterized. In the present study, in the spinal cord distal to the damaged area (perilesion perimeter) there were minimal gross histological changes, but there were pronounced alterations in the extracellular proteoglycans even at 30 days after SCI. These abnormalities coincided with the appearance of reactive astrocytes and a reduction in main astrocytic glutamate transporter 1. Proteoglycan levels exhibited different kinetics and changes after SCI in areas near neuronal cell bodies and in areas distal from them. The results of the study suggest that SCI induces widespread changes in the spinal cord that may be responsible for neuronal dysfunction far from the damaged area and further aggravation of the SCI.
The activity of supragranular pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) neurons is hypothesized to be a key contributor to the cellular basis of working memory in primates. ...Therefore, the intrinsic membrane properties, a crucial determinant of a neuron's functional properties, are important for the role of DLPFC pyramidal neurons in working memory. The present study aimed to investigate the biophysical properties of pyramidal cells in layer 2/3 of monkey DLPFC to create an unbiased electrophysiological classification of these cells. Whole cell voltage recordings in the slice preparation were performed in 77 pyramidal cells, and 24 electrophysiological measures of their passive and active intrinsic membrane properties were analyzed. Based on the results of cluster analysis of 16 independent electrophysiological variables, 4 distinct electrophysiological classes of monkey pyramidal cells were determined. Two classes contain regular-spiking neurons with low and high excitability and constitute 52% of the pyramidal cells sampled. These subclasses of regular-spiking neurons mostly differ in their input resistance, minimum current that evoked firing, and current-to-frequency transduction properties. A third class of pyramidal cells includes low-threshold spiking cells (17%), which fire a burst of three-five spikes followed by regular firing at all suprathreshold current intensities. The last class consists of cells with an intermediate firing pattern (31%). These cells have two modes of firing response, regular spiking and bursting discharge, depending on the strength of stimulation and resting membrane potential. Our results show that diversity in the functional properties of DLPFC pyramidal cells may contribute to heterogeneous modes of information processing during working memory and other cognitive operations that engage the activity of cortical circuits in the superficial layers of the DLPFC.
1 Departments of Psychiatry and 2 Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania
Submitted 11 December 2006;
accepted in final form 24 February 2007
The Cav2.1 (P/Q-) and Cav2.2 ...(N-type) voltage-gated calcium channels (VGCCs) play a predominant role in neurotransmitter release at central synapses, but their distribution is not uniform across different types of synapses. Although the functional significance of the differential distribution of N- and P/Q-type VGCCs is poorly understood, distinct types of VGCCs appear to differentially affect synaptic properties. For example, P/Q-type VGCCs are located closer to release sites and are less affected by G-protein-mediated inhibition than are N-type VGCCs. Thus P/Q-type VGCCs might be beneficial at synapses with high probability of release and precise timing of neurotransmission, such as the inhibitory inputs from parvalbumin-containing fast-spiking (FS) interneurons to pyramidal cells (PCs) in the neocortex. To determine whether VGCCs types predominate at synapses from FS interneurons to PCs in rat prefrontal cortex, whole cell paired recordings ( n = 14) combined with intracellular labeling and fluorescence immunohistochemistry for parvalbumin were performed in acute slices. Bath application of the specific N-type VGCC blocker -conotoxin-GVIa (1 µM) did not alter inhibitory postsynaptic potential amplitude, failure rate, or synaptic dynamics; in contrast, application of P/Q-type VGCC blocker -agatoxin-IVa (0.5 µM) completely and irreversibly blocked neurotransmission. These results indicate that P/Q-type VGCCs mediate the GABA release from parvalbumin-positive FS interneurons to PCs in the rat neocortex.
Address for reprint requests and other correspondence: A. V. Zaitsev, Dept. of Psychiatry, University of Pittsburgh School of Medicine, Room W1651, Biomedical Science Tower, 3811 O'Hara St., Pittsburgh, PA 15213-2593 (E-mail: zaitsevav{at}upmc.edu )
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 α-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.
1 Departments of Psychiatry and 2 Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania
Submitted 1 August 2006;
accepted in final form 14 November 2006
Current dogma holds that a ...canonical cortical circuit is formed by cellular elements that are basically identical across species. However, detailed and direct comparisons between species of specific elements of this circuit are limited in number. In this study, we compared the morphological and physiological properties of neurogliaform (NGF) inhibitory neurons in the prefrontal cortex (PFC) of macaque monkeys and rats. In both species, NGF cells were readily identified based on their distinctive morphological features. Indeed, monkey NGF cells had only a few morphological features that differed from rat, including a larger soma, a greater number of dendrites, and a more compact axonal field. In contrast, whole cell recordings of the responses to injected current steps revealed important differences between monkey and rat NGF cells. Monkey NGF cells consistently generated a short-latency first spike riding on an initial depolarizing hump, whereas in rat NGF cells, the first spike appeared after a substantial delay riding on a depolarizing ramp not seen in monkey NGF cells. Thus although rat NGF cells are traditionally classified as late-spiking cells, monkey NGF cells did not meet this physiological criterion. In addition, NGF cells in monkey appeared to be more excitable than those in rat because they displayed a higher input resistance, a lower spike threshold, and a higher firing frequency. Finally, NGF cells in monkey showed a more prominent spike-frequency adaptation as compared with rat. Our findings indicate that the canonical cortical circuit differs in at least some aspects of its constituent elements across species.
Address for reprint requests and other correspondence: N. V. Povysheva, Dept. of Psychiatry, University of Pittsburgh School of Medicine, Rm. W1651 Biomedical Science Tower, 3811 O'Hara St., Pittsburgh, PA 15213-2593 (E-mail: povyshevanv{at}upmc.edu )
1 Departments of Psychiatry, 2 Statistics, and 3 Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania
Submitted 14 February 2005;
accepted in final form 27 June 2005
In primates, little ...is known about intrinsic electrophysiological properties of neocortical neurons and their morphological correlates. To classify inhibitory cells (interneurons) in layers 23 of monkey dorsolateral prefrontal cortex we used whole cell voltage recordings and intracellular labeling in slice preparation with subsequent morphological reconstructions. Regular spiking pyramidal cells have been also included in the sample. Neurons were successfully segregated into three physiological clusters: regular-, intermediate-, and fast-spiking cells using cluster analysis as a multivariate exploratory technique. When morphological types of neurons were mapped on the physiological clusters, the cluster of regular spiking cells contained all pyramidal cells, whereas the intermediate- and fast-spiking clusters consisted exclusively of interneurons. The cluster of fast-spiking cells contained all of the chandelier cells and the majority of local, medium, and wide arbor (basket) interneurons. The cluster of intermediate spiking cells predominantly consisted of cells with the morphology of neurogliaform or vertically oriented (double-bouquet) interneurons. Thus a quantitative approach enabled us to demonstrate that intrinsic electrophysiological properties of neurons in the monkey prefrontal cortex define distinct cell types, which also display distinct morphologies.
Address for reprint requests and other correspondence: L. S. Krimer, Western Psychiatric Institute and Clinic, Biomedical Science Tower, W1651, 3811 O'Hara Street, Pittsburgh, PA 15213 (E-mail: krimerls{at}upmc.edu )
1 Departments of Psychiatry and 2 Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania
Submitted 4 August 2004;
accepted in final form 21 September 2004
Recent studies suggest that ...fast-spiking (FS) interneurons of the monkey dorsolateral prefrontal cortex (DLPFC) exhibit task-related firing during working-memory tasks. To gain further understanding of the functional role of FS neurons in monkey DLPFC, we described the in vitro electrophysiological properties of FS interneurons and their synaptic connections with pyramidal cells in layers 2/3 of areas 9 and 46. Extracellular spike duration was found to distinguish FS cells from non-FS interneuron subtypes. However, a substantial overlap in extracellular spike duration between these populations would make classification of individual interneurons difficult. FS neurons could be divided into two main morphological groups, chandelier and basket neurons, with very similar electrophysiological properties but significantly different horizontal spread of the axonal arborization. In paired cell recordings, unitary inhibitory postsynaptic potentials (IPSPs) elicited by FS neurons in pyramidal cells had rapid time course, small amplitude at resting membrane potential, and were mediated by GABA A receptors. Repetitive FS neuron stimulation, partially mimicking the sustained firing of interneurons in vivo, produced short-term depression of the unitary IPSPs, present at connections made by both basket and chandelier neurons and due at least in part to presynaptic mechanisms. These results suggest that FS neurons and their synaptic connections with pyramidal cells have homogeneous physiological properties. Thus different functional roles of basket and chandelier neurons in the DLPFC in vivo must arise from the distinct properties of the interneuronal axonal arborization or from a different functional pattern of excitatory and inhibitory connections with other components of the DLPFC neuronal network.
Address for reprint requests and other correspondence: G. González-Burgos, Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh School of Medicine, Room W1651 Biomedical Science Tower, 3811 O'Hara St., Pittsburgh, PA 15213-2593 (E-mail: gburgos{at}pitt.edu )
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