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.     

Study on function of aganglionic colon musculature of Hirschsprung's disease murine model

This study examined the function in vitro of aganglionic colon musculature in mice with hereditary aganglionosis--a strain of animals used as a model of Hirschsprung's disease. Double sucrose gap recordings from the muscle strips of both normal and aganglionic colon showed bursts of spike potentials with muscle contraction. Intracellular recordings of the membrane potentials of the circular muscle cells of normal, aganglionic and oligo-ganglionic colon had no statistical difference. Microelectrode recordings from the circular muscle cells of normal siblings, in the presence of nifedipine, irregular ongoing fluctuations in membrane potential, which were abolished by tetrodotoxin and reduced by d-tubocurarine or apamin. The fluctuations were less effected by atropine. These observations suggest that there is ongoing inhibitory neural activity to the circular smooth muscle of normal colon. These ongoing fluctuations were not recorded from the cells of aganglionic and oligo-ganglionic colon of affected animals. Although transmural stimulation of the intrinsic nerves produced cholinergic excitatory and inhibitory junction potentials in normal colon, no junction potentials were evoked by transmural stimulation in aganglionic colon. It was concluded that the ongoing tonic inhibitory activity may contribute to the compliance of the normal mouse colon and lack of the compliance may affect functional intestinal obstruction of the aganglionic colon in Hirschsprung's disease.     

Influence of low and high frequency inputs on spike timing in visual cortical neurons

Cortical neurons in vivo respond to sensory stimuli with the generation of action potentials that can show a high degree of variability in both their number and timing with repeated presentations as wells as, on occasion, a high degree of synchronization with other cortical neurons, including in the gamma frequency range of 30-70 Hz. Here we examined whether or not this variability may arise from the intrinsic mechanisms of action potential generation in cortical regular spiking, fast spiking and intrinsic burst-generating neurons maintained in vitro. For this purpose, we performed intracellular recordings in slices of ferret visual cortex and activated these cells with the intracellular injection of various current waveforms. Some of these waveforms were derived from barrages of postsynaptic potentials evoked by visual stimulation recorded in vivo; others were artificially created and contained various amounts of gamma range fluctuations; finally, others consisted of swept-sinewave current (ZAP current) functions. Using such stimuli, we found that, as expected given the resistive and capacitive properties of cortical neurons, low frequencies have a larger effect on the membrane potential of cortical neurons than do higher frequencies. However, increasing the amount of gamma range fluctuations in a stimulus leads to more precise timing of action potentials. This suggests that different frequencies play different roles, low frequencies being efficient for depolarizing cells with high frequencies increasing the precision of action potential timing. In parallel to increases in temporal precision, the addition of higher frequency components increases the range of interspike intervals present in the action potential discharge. These results suggest that higher frequency components such as gamma range fluctuations may facilitate the generation of action potentials with a high temporal precision while at the same time exhibiting a high degree of variability in interspike intervals on single trials. This temporal precision may facilitate the use of temporal codes or the generation of precise synchronization for the transmission and analysis of information within cortical networks.      

A cellular correlate of learning-induced metaplasticity in the hippocampus

Metaplasticity, the plasticity of synaptic plasticity, is thought to have a pivotal role in activity-dependent modulation of synaptic connectivity, which underlies learning and memory. Metaplasticity is usually attributed to modifications in glutamate receptor-mediated synaptic transmission. However, experimental evidence and theoretical considerations suggest that learning reduces the predisposition for further synaptic strengthening, while behavioral studies show that learning capability is enhanced by prior learning. Here we show that enhanced neuronal excitability in CA1 pyramidal neurons, but not enhanced synaptic transmission, occurs prior to rule learning of an olfactory discrimination task. This transient enhancement lasts for 1 day after rule learning, is apparent throughout the cell population and results from reduction in the medium and slow after-hyperpolarizations that control spike frequency adaptation. Such olfactory learning-induced increased excitability in hippocampal neurons enhances the rats' learning capability in another hippocampus-dependent task, the Morris water maze. Once olfactory discrimination rule learning is acquired, its maintenance is not dependent on the reduced post-burst AHP in hippocampal neurons. However, the enhanced spatial learning capability of olfactory-trained rats in the water maze is diminished once the post burst AHP in CA1 pyramidal cells resumes its initial value. We suggest that enhanced excitability of CA1 neurons may serve as a mechanism for generalized enhancement of hippocampus-dependent learning capability. In the presence of such enhanced neuronal excitability, the hippocampal network enters into a 'learning mode' in which a variety of hippocampus-dependent skills are acquired rapidly and efficiently.     

An electrophysiological study of the smooth muscle of the human colon.

Electrical recordings were made in vitro from preparations of human colonic smooth muscle from surgically resected specimens. The behaviour of the taenia consisted of regular spike action potentials based on a slow wave rhythm (22 +/- 5 c.p.m.), with tetanic contractions of the muscle. The actions of cholinergic drugs were studied and experiments performed to investigate the mechanism of the action potentials. The circular muscle produced clusters of spikes with solitary contractions. The differences between the two muscle layers may be of relevance to understanding the colonic electromyogram as recorded in vivo.     

Sevoflurane blocks cholinergic synaptic transmission postsynaptically but does not affect short-term potentiation

BACKGROUND: As compared with their effects on both inhibitory and excitatory synapses, little is known about the mechanisms by which general anesthetics affect synaptic plasticity that forms the basis for learning and memory at the cellular level. To test whether clinically relevant concentrations of sevoflurane affect short-term potentiation involving cholinergic synaptic transmission, the soma-soma synapses between identified, postsynaptic neurons were used. METHODS: Uniquely identifiable neurons visceral dorsal 4 (presynaptic) and left pedal dorsal 1 (postsynaptic) of the mollusk Lymnaea stagnalis were isolated from the intact ganglion and paired overnight in a soma-soma configuration. Simultaneous intracellular recordings coupled with fluorescent imaging of the FM1-43 dye were made in either the absence or the presence of sevoflurane. RESULTS: Cholinergic synapses, similar to those observed in vivo, developed between the neurons, and the synaptic transmission exhibited classic short-term, posttetanic potentiation. Action potential-induced (visceral dorsal 4), 1:1 excitatory postsynaptic potentials were reversibly and significantly suppressed by sevoflurane in a concentration-dependent manner. Fluorescent imaging with the dye FM1-43 revealed that sevoflurane did not affect presynaptic exocytosis or endocytosis; instead, postsynaptic nicotinic acetylcholine receptors were blocked in a concentration-dependent manner. To test the hypothesis that sevoflurane affects short-term potentiation, a posttetanic potentiation paradigm was used, and synaptic transmission was examined in either the presence or the absence of sevoflurane. Although 1.5% sevoflurane significantly reduced synaptic transmission between the paired cells, it did not affect the formation or retention of posttetanic potentiation at this synapse. CONCLUSIONS: This study demonstrates that sevoflurane blocks cholinergic synaptic transmission postsynaptically but does not affect short-term synaptic plasticity at the visceral dorsal 4-left pedal dorsal 1 synapse.     

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.     

Association of learning and memory impairments with changes in the septohippocampal cholinergic system in rats with kaolin-induced hydrocephalus

OBJECTIVE: The septohippocampal cholinergic (SHC) system plays an important role in the maintenance of normal memory and learning. However, the fact that memory and learning impairments under hydrocephalic conditions are directly related to the SHC system is less well known. We investigated the relationships between pathological changes in SHC neurons and impairments in memory and learning among hydrocephalic rats. METHODS: Rats with kaolin-induced hydrocephalus were prepared with injections of kaolin suspension into the cisterna magna. Learning and memory performance was assessed with the passive avoidance and Morris water maze tests. Ventricular sizes were measured for the lateral and third ventricles. Acetylcholinesterase and choline acetyltransferase immunostaining was performed to investigate degenerative changes in cholinergic neurons in the medial septum and hippocampus. RESULTS: Hydrocephalic rats demonstrated significant learning and memory impairments in the passive avoidance and Morris water maze tests. Decreased hesitation times in the passive avoidance test and markedly increased acquisition times and decreased retention times in the Morris water maze test indicated learning and memory dysfunction among the hydrocephalic rats. The numbers of cholinergic neurons in the medial septum and hippocampus were decreased in the hydrocephalic rats. The decreases in choline acetyltransferase and acetylcholinesterase immunoreactivity were significantly correlated with enlargement of the ventricles. CONCLUSION: Impairment of spatial memory and learning may be attributable to degeneration of SHC neurons. These results suggest that learning and memory impairments in rats with kaolin-induced hydrocephalus are associated with the dysfunction of the SHC system induced by ventricular dilation.     

Synaptic basis of persistent activity in prefrontal cortex in vivo and in organotypic cultures

Persistent activity is observed in many cortical and subcortical brain regions, and may subserve a variety of functions. Within the prefrontal cortex (PFC), neurons transiently maintain information in working memory via persistent activity patterns; however, the mechanisms involved are largely unknown. The present study used intracellular recordings from deep layer PFC neurons in vivo and patch-clamp recordings from PFC neurons in organotypic brain slice cultures to examine the ionic mechanisms underlying persistent activity states evoked by various inputs. Persistent activity had consistent features regardless of the initiating stimulus; it was driven by non-NMDA glutamate receptors yet consisted of an initial GABA mediated component, followed by a prolonged synaptically mediated inward current that maintained the sustained depolarization on which rode many asynchronous GABA-mediated events. The stereotyped nature of the multiple-component persistent activity pattern reported here might be a common feature of interconnected cortical networks but within PFC could be related to the persistent activity required for working memory.     

Sevoflurane Blocks Cholinergic Synaptic Transmission Postsynaptically but Does Not Affect Short-term Potentiation

Background: As compared with their effects on both inhibitory and excitatory synapses, little is known about the mechanisms by which general anesthetics affect synaptic plasticity that forms the basis for learning and memory at the cellular level. To test whether clinically relevant concentrations of sevoflurane affect short-term potentiation involving cholinergic synaptic transmission, the soma-soma synapses between identified, postsynaptic neurons were used.

Methods: Uniquely identifiable neurons visceral dorsal 4 (presynaptic) and left pedal dorsal 1 (postsynaptic) of the mollusk Lymnaea stagnalis were isolated from the intact ganglion and paired overnight in a soma-soma configuration. Simultaneous intracellular recordings coupled with fluorescent imaging of the FM1-43 dye were made in either the absence or the presence of sevoflurane.

Results: Cholinergic synapses, similar to those observed in vivo, developed between the neurons, and the synaptic transmission exhibited classic short-term, posttetanic potentiation. Action potential-induced (visceral dorsal 4), 1:1 excitatory postsynaptic potentials were reversibly and significantly suppressed by sevoflurane in a concentration-dependent manner. Fluorescent imaging with the dye FM1-43 revealed that sevoflurane did not affect presynaptic exocytosis or endocytosis; instead, postsynaptic nicotinic acetylcholine receptors were blocked in a concentration-dependent manner. To test the hypothesis that sevoflurane affects short-term potentiation, a posttetanic potentiation paradigm was used, and synaptic transmission was examined in either the presence or the absence of sevoflurane. Although 1.5% sevoflurane significantly reduced synaptic transmission between the paired cells, it did not affect the formation or retention of posttetanic potentiation at this synapse.     

Halothane, but not the nonimmobilizers perfluoropentane and 1,2-dichlorohexafluorocyclobutane, depresses synaptic transmission in hippocampal CA1 neurons in rats.

Volatile anesthetics may decrease synaptic transmission at central neurons by presynaptic and/or postsynaptic actions. Nonimmobilizers are volatile compounds with lipophilicities that suggest that they should (but do not) prevent motor responses to surgical stimuli. However, nonimmobilizers interfere with learning and memory, and, thus, might be predicted to depress synaptic transmission in areas of the brain mediating memory (e.g., hippocampal CA1 neurons). To test this possibility, we stimulated the Schaffer collaterals of rat hippocampal slices and recorded from stratum pyramidale of CA1 neurons. At approximately 0.5 MAC (MAC is the minimum alveolar anesthetic concentration at one standard atmosphere that is required to eliminate movement in response to noxious stimulation in 50% of subjects), halothane decreased population spike amplitude 37% +/- 21% (mean +/- SD), increased latency 15% +/- 9%, and decreased excitatory postsynaptic potentials 16% +/- 10%. In contrast, at concentrations below (0.4 times) predicted MAC, the nonimmobilizer, 1,2 dichlorohexafluorocyclobutane (2N), slightly (not significantly) increased population spike amplitude, decreased population spike latency 9% +/- 4%, and increased excitatory postsynaptic potentials 22% +/- 16%. At concentrations above (2 times) predicted MAC, 2N did not significantly increase population spike, decreased latency 10% +/- 4%, and did not significantly change excitatory postsynaptic potentials. At 0.1 predicted MAC, a second nonimmobilizer, perfluoropentane, tended (P = 0.05) to increase (11% +/- 9%) population spike amplitude, decreased population spike latency 8% +/- 2%, and tended (P = 0.06) to increase excitatory postsynaptic potentials (9% +/- 8%). We conclude that clinically relevant concentrations of halothane depress synaptic transmission at Schaffer collateral-CA1 synapses and that the nonimmobilizers 2N and perfluoropentane have no effect or are excitatory. The Schaffer collateral-CA1 synapse may serve as a useful model for the production of immobility by volatile anesthetics, but is flawed as a model for the capacity of volatile anesthetics to interfere with memory and learning. IMPLICATIONS: Halothane, but not the nonimmobilizers 1,2-dichlorohexafluorocyclobutane and perfluoropentane, inhibits hippocampal synaptic transmission at Schaffer collateral-CA1 synapses.     

Spontaneous synaptic activity of subplate neurons in neonatal rat somatosensory cortex

Subplate neurons play an important role in early cortical development. To investigate whether these transient neurons receive synaptic inputs, we performed whole-cell recordings from visually identified and biocytin-labeled subplate cells in somatosensory cortical slices from postnatal day 0-3 rats. Subplate neurons had an average resting membrane potential of -55 mV and input resistance of approximately 1.1 G ohms. Suprathreshold current injection elicited in 67% of the cells repetitive action potentials at 4-13 Hz and the remaining 33% showed only one spike. Three classes of spontaneous postsynaptic currents (sPSCs) could be identified: (i) Fast sPSCs, with an average amplitude of 14 pA and a decay time of 6.3 ms, which showed a 95% decrease in their frequency during (+/-)-gamma-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate receptor blockade. Cyclothiazide caused a 3.5-fold increase in the decay time, indicating that fast sPSCs were mediated by AMPA receptors. (ii) Slow sPSCs, with 18 pA amplitude and 51.2 ms decay time were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist CPP. (iii) Chloride-driven sPSCs, with 34.4 pA amplitude and 123 ms decay time that were blocked by the gamma-amino-butyric acid A (GABA(A)) receptor antagonist gabazine. While tetrodotoxin citrate (TTX) blocked completely NMDA-mediated slow sPSCs, the frequency of AMPA- and GABA(A)-mediated sPSCs was reduced in TTX by 55 and 90%, respectively. These results indicate that subplate neurons receive functional synaptic inputs mediated by AMPA, NMDA and GABA(A) receptors.     

An intracellular study of the contrast-dependence of neuronal activity in cat visual cortex

Extracellular recordings indicate that mechanisms that control contrast gain of neuronal discharge are found in the retina, thalamus and cortex. In addition, the cortex is able to adapt its contrast response function to match the average local contrast. Here we examine the neuronal mechanism of contrast adaptation by direct intracellular recordings in vivo. Both simple (n = 3) and complex cells (n = 4) show contrast adaptation during intracellular recording. For simple cells, that the amplitude of fluctuations in membrane potential induced by a drifting grating stimulus follows a contrast response relation similar to lateral geniculate relay cells, and does not reflect the high gain and adaptive properties seen in the action potential discharge of the neurons. We found no evidence of significant shunting inhibition that could explain these results. In complex cells there was no change in the mean membrane potential for different contrast stimuli or different states of adaptation, despite marked changes in discharge rate. We use a simplified electronic model to discuss the central features of our results and to explain the disparity between the contrast response functions of the membrane potential and action potential discharge in simple cells.      

Activity-dependent modulation of synaptic transmission in the intact human motor cortex revealed with transcranial magnetic stimulation

Activity-dependent modulation of cortical synaptic transmission is a fundamental mechanism involved in learning and memory storage. This modulation has been widely studied in in vitro brain slices and in vivo animal models. More recently, transcranial magnetic stimulation has allowed detection of activity-dependent excitability modulation occurring in the intact human primary motor cortex (MI) after execution of different kinds of motor tasks. Both increased and decreased MI excitability have been described after exercise. While increased MI excitability is generally considered direct expression of cortical synaptic plasticity, a controversy still exists as to whether decreased MI excitability reflects fatigue of central nervous system (CNS) structures or cortical neuronal reorganization taking place after exercise. Here, we extend previous findings in order to provide further support for the latter hypothesis. Abduction- adduction movements of the thumb performed for 1 min at 2 Hz frequency rate produce a 55% decrease in MI excitability of mean 30 min duration. Similar decrements in amplitude and duration of motor evoked potentials (MEPs) are not reached if the same task is performed once again during the maximal inhibition phase (10 min post-exercise) produced by a previous activation. Moreover, the same task performed at a lower (1 Hz) frequency rate produces no significant MEP changes but can transiently reverse activity-dependent depression obtained after previous 2 Hz movements. Repeated execution of the same task (2 Hz), each being performed after recovery from a previously induced MEP depression, ceases to produce an MEP decrement, suggesting adaptation in MI excitability modulation. This adaptation is long lasting and task-specific, since a different motor task (1 min circular movement of the thumb) restores activity-dependent modulation. Overall, these findings suggest that the dynamic modulation of MEPs occurring after execution of different kinds of simple motor skills reflects some form of activity-dependent, plastic neuronal reorganization instead of CNS fatigue. Possible anatomo-functional mechanisms involved in this activity-dependent modulation of MI excitability are discussed.     

Intraretrosplenial cortical grafts of fetal cholinergic neurons and the restoration of spatial memory function

The retrosplenial cortex (RSC) receives cholinergic afferent fibers from the medial septal nucleus and diagonal band of Broca (DBB) by way of the cingulate bundle and the fornix. Bilateral lesions of both the cingulate and fornix pathways result in a complete depletion of cholinergic input to the RSC. In the present study we have examined the effects of transplanting cholinergic neurons from fetal rat pups to the RSC of adult rats following lesions of the cingulate bundle and fornix. The animals with lesions exhibited severe spatial memory impairments with a complete loss of extrinsic cholinergic afferents to the RSC. Animals with intraretrosplenial cortical transplants exhibited significant improvements in learning and memory performance as revealed by decreased escape latencies in spatial reference memory tests, increased numbers of platform crossings in spatial navigation tests, and a higher percentage of correct choices in a spatial working memory task. These improvements appeared to be cholinergically mediated because atropine administration significantly disrupted spatial navigation performance. The survival of the transplanted cholinergic neurons and their innervation of the RSC were characterized using a monoclonal antibody to choline acetyltransferase (ChAT). The staining of graft-derived ChAT-positive fibers also revealed a pattern of innervation that mimicked that of the cholinergic input in normal animals. These results indicate that intraretrosplenial cortical transplants of cholinergic neurons can rectify spatial memory deficits produced by the loss of intrinsic cholinergic afferents from the medial septal nucleus.     

Synaptic efficacy during repetitive activation of excitatory inputs in primate dorsolateral prefrontal cortex

Neurons in the monkey dorsolateral prefrontal cortex (DLPFC) fire persistently during the delay period of working memory tasks. To determine how repetitive firing affects the efficacy of synaptic inputs to DLPFC layer 3 neurons, we examined the effects of repetitive presynaptic stimulation on the amplitude and temporal summation of EPSPs. Recordings were obtained in monkey DLPFC brain slices from regular spiking (RS) pyramidal cells and two types of interneurons, fast spiking (FS) and adapting non-pyramidal (ANP) cells. Repetitive stimulation of presynaptic axons in layer 3 caused EPSP depression in RS and FS neurons, but EPSP facilitation in ANP cells. A shorter EPSP duration produced weaker temporal summation in FS neurons compared to the other cell classes. Thus, due to the combined effects of dynamic changes in EPSP amplitude and differences in temporal summation, the effect of a presynaptic spike train differed according to the postsynaptic cell class. Similar results were obtained when recording unitary EPSPs evoked in connected pairs of presynaptic RS pyramidal cells and postsynaptic RS, FS or ANP neurons. In addition, similar differences in the efficacy of sustained inputs among cell classes were observed when delay-related firing was reproduced in vitro by stimulating inputs with the timing of spike trains recorded from the DLPFC of monkeys performing a delayed-response task. We suggest that the transition from baseline firing rates to higher frequency delay-related firing may lead to the differential activation of distinct cell populations, with corresponding significant effects on the patterns of activity in local prefrontal circuits.     

Relationship between EEG potentials and intracellular activity of striatal and cortico-striatal neurons: an in vivo study under different anesthetics

The functions of the basal ganglia are achieved through excitation of striatal output neurons (SONs) by converging cortical glutamergic afferents. We assessed the relationship between different patterns of activity in cortico-striatal (C-S) cells and the electrical behavior of SONs in vivo. Intracellular activities of rat C-S neurons in the orofacial motor cortex and of SONs, located in the projection field of this cortical region, were recorded under different anesthetics, which generate various temporal patterns of cortical activity. A surface electroencephalogram (EEG) of the orofacial motor cortex was simultaneously performed with intracellular recordings and EEG waves were used as correlates of a coherent synaptic activity in cortical neurons. Under barbiturate anesthesia C-S neurons showed rhythmic (5--7 Hz) supra-threshold depolarizations in phase with large amplitude EEG waves. The correlative activity of SONs was characterized by large amplitude oscillation-like synaptic depolarizations that could trigger action potentials. Under ketamine-xylazine anesthesia C-S neurons exhibited a step-like behavior consisting of depolarizing plateaus (up states), leading to multiple spike discharges, interrupted by hyperpolarizing periods (down states). The related activity of SONs was step-like membrane potential fluctuations with firing confined to the early part of the striatal up state. In C-S neurons and SONs up states coincided with slow recurrent EEG waves (approximately 1 Hz). Finally, under neurolept-analgesia an apparently disorganized EEG activity was associated with a lack of rhythmic discharge in C-S neurons. This uncorrelated activity in C-S neurons resulted in an absence of spontaneous firing as well as of large amplitude synaptic depolarizations in SONs. In the present study we demonstrate that SONs shape their input-output relationship by filtering out uncorrelated synaptic activity and that a minimal synchronization in the cortico-striatal afferents is required to produce significant synaptic depolarization in SONs.     

Origin of slow cortical oscillations in deafferented cortical slabs

An in vivo preparation has been developed to study the mechanisms underlying spontaneous sleep oscillations. Dual and triple simultaneous intracellular recordings were made from neurons in small isolated cortical slabs (10 mm x 6 mm) in anesthetized cats. Spontaneously occurring slow sleep oscillations, present in the adjacent intact cortex, were absent in small slabs. However, the isolated slabs displayed brief active periods separated by long periods of silence, up to 60 s in duration. During these silent periods, 60% of neurons showed non-linear amplification of low-amplitude depolarizing activity. Nearly 40% of the cells, twice as many as in intact cortex, were classified as intrinsically bursting. In cortical network models based on Hodgkin-Huxley-like neurons, the summation of simulated spontaneous miniature excitatory postsynaptic potentials was sufficient to activate a persistent sodium current, initiating action potentials in single neurons that then spread through the network. Consistent with this model, enlarging the isolated cortical territory to an isolated gyrus (30 mm x 20 mm) increased the probability of initiating large-scale activity. In these larger territories, both the frequency and regularity of the slow oscillation approached that generated in intact cortex. The frequency of active periods in an analytical model of the cortical network accurately predicted the scaling observed in simulations and from recordings in cortical slabs of increasing size.     

Neurotransmitter release from high-frequency stimulation of the subthalamic nucleus

OBJECT: High-frequency stimulation (HFS) delivered through implanted electrodes in the subthalamic nucleus (STN) has become an established treatment for Parkinson disease (PD). The precise mechanism of action of deep brain stimulation (DBS) in the STN is unknown, however. In the present study, the authors tested the hypothesis that HFS within the STN changes neuronal action potential firing rates during the stimulation period by modifying neurotransmitter release. METHODS: Intracellular electrophysiological recordings were obtained using sharp electrodes in rat STN neurons in an in vitro slice preparation. A concentric bipolar stimulating electrode was placed in the STN slice, and electrical stimulation (pulse width 50-100 microsec, duration 100-2000 msec, amplitude 10-500 microA, and frequency 10-200 Hz) was delivered while simultaneously obtaining intracellular recordings from an STN neuron. High-frequency stimulation of the STN either generated excitatory postsynaptic potentials (EPSPs) and increased the action potential frequency or it generated inhibitory postsynaptic potentials and decreased the action potential frequency of neurons within the STN. These effects were blocked after antagonists to glutamate and gamma-aminobutyric acid were applied to the tissue slice, indicating that HFS resulted in the release of neurotransmitters. Intracellular recordings from substantia nigra pars compacta (SNc) dopaminergic neurons during HFS of the STN revealed increased generation of EPSPs and increased frequency of action potentials in SNc neurons. CONCLUSIONS: During HFS of STN neurons the mechanism of DBS may involve the release of neurotransmitters rather than the primary electrogenic inhibition of neurons.     

Spectrotemporal receptive fields in anesthetized cat primary auditory cortex are context dependent

In order to investigate how the auditory scene is analyzed and perceived, auditory spectrotemporal receptive fields (STRFs) are generally used as a convenient way to describe how frequency and temporal sound information is encoded. However, using broadband sounds to estimate STRFs imperfectly reflects the way neurons process complex stimuli like conspecific vocalizations insofar as natural sounds often show limited bandwidth. Using recordings in the primary auditory cortex of anesthetized cats, we show that presentation of narrowband stimuli not including the best frequency of neurons provokes the appearance of residual peaks and increased firing rate at some specific spectral edges of stimuli compared with classical STRFs obtained from broadband stimuli. This result is the same for STRFs obtained from both spikes and local field potentials. Potential mechanisms likely involve release from inhibition. We thus emphasize some aspects of context dependency of STRFs, that is, how the balance of inhibitory and excitatory inputs is able to shape the neural response from the spectral content of stimuli.