(1/13503) Trans-synaptically induced bursts in regular spiking non-pyramidal cells in deep layers of the cat motor cortex.
In deep layers of the cat motor cortex, we have investigated the properties of neurons displaying trans-synaptically induced bursts. In in vivo experiments, extracellularly recorded burst neurons were separated into two subtypes based on their dependence on stimulation sites, the medullary pyramid or the ventrolateral (VL) thalamic nucleus, from which bursts of 10-20 spikes were triggered. The spike amplitude attenuation and frequency adaptation during a burst were more prominent in pyramid-dependent burst neurons than in VL-dependent burst neurons. Intracellular recordings in in vivo experiments revealed that pyramid-dependent bursts emerged from a long-lasting depolarization, while each spike during a VL-dependent burst was narrow in half-width and was followed by a fast AHP, similar to fast spiking neurons. In in vitro slice experiments, intracellular recordings were obtained from neurons that displayed a burst of attenuated spikes emerging from a long-lasting depolarization, and were also obtained from fast spiking neurons. They were morphologically recovered to be multipolar cells with sparsely spiny dendrites and local axonal networks, suggesting that they are inhibitory interneurons. The multipolar neurons displaying bursts of attenuated spikes may mediate the recurrent inhibition of pyramidal tract cells. (+info)
(2/13503) Developmental synaptic changes increase the range of integrative capabilities of an identified excitatory neocortical connection.
Excitatory synaptic transmission between pyramidal cells and fast-spiking (FS) interneurons of layer V of the motor cortex was investigated in acute slices by using paired recordings at 30 degrees C combined with morphological analysis. The presynaptic and postsynaptic properties at these identified central synapses were compared between 3- and 5-week-old rats. At these two postnatal developmental stages, unitary EPSCs were mediated by the activation of AMPA receptors with fast kinetics at a holding potential of -72 mV. The amplitude distribution analysis of the EPSCs indicates that, at both stages, pyramidal-FS connections consisted of multiple functional release sites. The apparent quantal size obtained by decreasing the external calcium ([Ca2+]e) varied from 11 to 29 pA near resting membrane potential. In young rats, pairs of presynaptic action potentials elicited unitary synaptic responses that displayed paired-pulse depression at all tested frequencies. In older animals, inputs from different pyramidal cells onto the same FS interneuron had different paired-pulse response characteristics and, at most of these connections, a switch from depression to facilitation occurred when decreasing the rate of presynaptic stimulation. The balance between facilitation and depression endows pyramidal-FS connections from 5-week-old animals with wide integrative capabilities and confers unique functional properties to each synapse. (+info)
(3/13503) Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine.
In a slice preparation of rat visual cortex, we discovered that paired-pulse stimulation (PPS) elicits a form of homosynaptic long-term depression (LTD) in the superficial layers when carbachol (CCh) or norepinephrine (NE) is applied concurrently. PPS by itself, or CCh and NE in the absence of synaptic stimulation, produced no lasting change. The LTD induced by PPS in the presence of NE or CCh is of comparable magnitude with that obtained with prolonged low-frequency stimulation (LFS) but requires far fewer stimulation pulses (40 vs 900). The cholinergic facilitation of LTD was blocked by atropine and pirenzepine, suggesting involvement of M1 receptors. The noradrenergic facilitation of LTD was blocked by urapidil and was mimicked by methoxamine, suggesting involvement of alpha1 receptors. beta receptor agonists and antagonists were without effect. Induction of LTD by PPS was inhibited by NMDA receptor blockers (completely in the case of NE; partially in the case of CCh), suggesting that one action of the modulators is to control the gain of NMDA receptor-dependent homosynaptic LTD in visual cortex. We propose that this is a mechanism by which cholinergic and noradrenergic inputs to the neocortex modulate naturally occurring receptive field plasticity. (+info)
(4/13503) Plasticity of first-order sensory synapses: interactions between homosynaptic long-term potentiation and heterosynaptically evoked dopaminergic potentiation.
Persistent potentiations of the chemical and electrotonic components of the eighth nerve (NVIII) EPSP recorded in vivo in the goldfish reticulospinal neuron, the Mauthner cell, can be evoked by afferent tetanization or local dendritic application of an endogenous transmitter, dopamine (3-hydroxytyramine). These modifications are attributable to the activation of distinct intracellular kinase cascades. Although dopamine-evoked potentiation (DEP) is mediated by the cAMP-dependent protein kinase (PKA), tetanization most likely activates a Ca2+-dependent protein kinase via an increased intracellular Ca2+ concentration. We present evidence that the eighth nerve tetanus that induces LTP does not act by triggering dopamine release, because it is evoked in the presence of a broad spectrum of dopamine antagonists. To test for interactions between these pathways, we applied the potentiating paradigms sequentially. When dopamine was applied first, tetanization produced additional potentiation of the mixed synaptic response, but when the sequence was reversed, DEP was occluded, indicating that the synapses potentiated by the two procedures belong to the same or overlapping populations. Experiments were conducted to determine interactions between the underlying regulatory mechanisms and the level of their convergence. Inhibiting PKA does not impede tetanus-induced LTP, and chelating postsynaptic Ca2+ with BAPTA does not block DEP, indicating that the initial steps of the induction processes are independent. Pharmacological and voltage-clamp analyses indicate that the two pathways converge on functional AMPA/kainate receptors for the chemically mediated EPSP and gap junctions for the electrotonic component or at intermediaries common to both pathways. A cellular model incorporating these interactions is proposed on the basis of differential modulation of synaptic responses via receptor-protein phosphorylation. (+info)
(5/13503) Cellular sites for dynorphin activation of kappa-opioid receptors in the rat nucleus accumbens shell.
The nucleus accumbens (Acb) is prominently involved in the aversive behavioral aspects of kappa-opioid receptor (KOR) agonists, including its endogenous ligand dynorphin (Dyn). We examined the ultrastructural immunoperoxidase localization of KOR and immunogold labeling of Dyn to determine the major cellular sites for KOR activation in this region. Of 851 KOR-labeled structures sampled from a total area of 10,457 microm2, 63% were small axons and morphologically heterogenous axon terminals, 31% of which apposed Dyn-labeled terminals or also contained Dyn. Sixty-eight percent of the KOR-containing axon terminals formed punctate-symmetric or appositional contacts with unlabeled dendrites and spines, many of which received convergent input from terminals that formed asymmetric synapses. Excitatory-type terminals that formed asymmetric synapses with dendritic spines comprised 21% of the KOR-immunoreactive profiles. Dendritic spines within the neuropil were the major nonaxonal structures that contained KOR immunoreactivity. These spines also received excitatory-type synapses from unlabeled terminals and were apposed by Dyn-containing terminals. These results provide ultrastructural evidence that in the Acb shell (AcbSh), KOR agonists play a primary role in regulating the presynaptic release of Dyn and other neuromodulators that influence the output of spiny neurons via changes in the presynaptic release of or the postsynaptic responses to excitatory amino acids. The cellular distribution of KOR complements those described previously for the reward-associated mu- and delta-opioid receptors in the Acb shell. (+info)
(6/13503) GABAergic excitatory synapses and electrical coupling sustain prolonged discharges in the prey capture neural network of Clione limacina.
Afterdischarges represent a prominent characteristic of the neural network that controls prey capture reactions in the carnivorous mollusc Clione limacina. Their main functional implication is transformation of a brief sensory input from a prey into a lasting prey capture response. The present study, which focuses on the neuronal mechanisms of afterdischarges, demonstrates that a single pair of interneurons [cerebral A interneuron (Cr-Aint)] is responsible for afterdischarge generation in the network. Cr-Aint neurons are electrically coupled to all other neurons in the network and produce slow excitatory synaptic inputs to them. This excitatory transmission is found to be GABAergic, which is demonstrated by the use of GABA antagonists, uptake inhibitors, and double-labeling experiments showing that Cr-Aint neurons are GABA-immunoreactive. The Cr-Aint neurons organize three different pathways in the prey capture network, which provide positive feedback necessary for sustaining prolonged spike activity. The first pathway includes electrical coupling and slow chemical transmission from the Cr-Aint neurons to all other neurons in the network. The second feedback is based on excitatory reciprocal connections between contralateral interneurons. Recurrent excitation via the contralateral cell can sustain prolonged interneuron firing, which then drives the activity of all other cells in the network. The third positive feedback is represented by prominent afterdepolarizing potentials after individual spikes in the Cr-Aint neurons. Afterdepolarizations apparently represent recurrent GABAergic excitatory inputs. It is suggested here that these afterdepolarizing potentials are produced by GABAergic excitatory autapses. (+info)
(7/13503) A genetic approach to visualization of multisynaptic neural pathways using plant lectin transgene.
The wiring patterns among various types of neurons via specific synaptic connections are the basis of functional logic employed by the brain for information processing. This study introduces a powerful method of analyzing the neuronal connectivity patterns by delivering a tracer selectively to specific types of neurons while simultaneously transsynaptically labeling their target neurons. We developed a novel genetic approach introducing cDNA for a plant lectin, wheat germ agglutinin (WGA), as a transgene under the control of specific promoter elements. Using this method, we demonstrate three examples of visualization of specific transsynaptic neural pathways: the mouse cerebellar efferent pathways, the mouse olfactory pathways, and the Drosophila visual pathways. This strategy should greatly facilitate studies on the anatomical and functional organization of the developing and mature nervous system. (+info)
(8/13503) Single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hippocampal dendritic spines.
We have used confocal microscopy to monitor synaptically evoked Ca2+ transients in the dendritic spines of hippocampal pyramidal cells. Individual spines respond to single afferent stimuli (<0.1 Hz) with Ca2+ transients or failures, reflecting the probability of transmitter release at the activated synapse. Both AMPA and NMDA glutamate receptor antagonists block the synaptically evoked Ca2+ transients; the block by AMPA antagonists is relieved by low Mg2+. The Ca2+ transients are mainly due to the release of calcium from internal stores, since they are abolished by antagonists of calcium-induced calcium release (CICR); CICR antagonists, however, do not depress spine Ca2+ transients generated by backpropagating action potentials. These results have implications for synaptic plasticity, since they show that synaptic stimulation can activate NMDA receptors, evoking substantial Ca2+ release from the internal stores in spines without inducing long-term potentiation (LTP) or depression (LTD). (+info)