Characterization of thalamocortical responses of regular-spiking and fast-spiking neurons of the mouse auditory cortex in vitro and in silico

We use a combination of in vitro whole cell recordings and computer simulations to characterize the cellular and synaptic properties that contribute to processing of auditory stimuli. Using a mouse thalamocortical slice preparation, we record the intrinsic membrane properties and synaptic properties of layer 3/4 regular-spiking (RS) pyramidal neurons and fast-spiking (FS) interneurons in primary auditory cortex (AI). We find that postsynaptic potentials (PSPs) evoked in FS cells are significantly larger and depress more than those evoked in RS cells after thalamic stimulation. We use these data to construct a simple computational model of the auditory thalamocortical circuit and find that the differences between FS and RS cells observed in vitro generate model behavior similar to that observed in vivo. We examine how feedforward inhibition and synaptic depression affect cortical responses to time-varying inputs that mimic sinusoidal amplitude-modulated tones. In the model, the balance of cortical inhibition and thalamic excitation evolves in a manner that depends on modulation frequency (MF) of the stimulus and determines cortical response tuning.     

Synaptic interactions between thalamic and cortical inputs onto cortical neurons in vivo

To study the interactions between thalamic and cortical inputs onto neocortical neurons, we used paired-pulse stimulation (PPS) of thalamic and cortical inputs as well as PPS of two cortical or two thalamic inputs that converged, at different time intervals, onto intracellularly recorded cortical and thalamocortical neurons in anesthetized cats. PPS of homosynaptic cortico-cortical pathways produced facilitation, depression, or no significant effects in cortical pathways, whereas cortical responses to thalamocortical inputs were mostly facilitated at both short and long intervals. By contrast, heterosynaptic interactions between either cortical and thalamic, or thalamic and cortical, inputs generally produced decreases in the peak amplitudes and depolarization area of evoked excitatory postsynaptic potentials (EPSPs), with maximal effect at approximately 10 ms and lasting from 60 to 100 ms. All neurons tested with thalamic followed by cortical stimuli showed a decrease in the apparent input resistance (R(in)), the time course of which paralleled that of decreased responses, suggesting that shunting is the factor accounting for EPSP's decrease. Only half of neurons tested with cortical followed by thalamic stimuli displayed changes in R(in). Spike shunting in the thalamus may account for those cases in which decreased synaptic responsiveness of cortical neurons was not associated with decreased R(in) because thalamocortical neurons showed decreased firing probability during cortical stimulation. These results suggest a short-lasting but strong shunting between thalamocortical and cortical inputs onto cortical neurons.     

Differential response dynamics of corticothalamic glutamatergic synapses in the lateral geniculate nucleus and thalamic reticular nucleus

The corticothalamic feedback pathway provides excitatory synaptic input to both the thalamic reticular nucleus and the lateral geniculate nucleus. We studied excitatory postsynaptic currents elicited from corticothalamic stimulation in the visual sector of the thalamic reticular nucleus and the lateral geniculate nucleus to compare the response of these neurons to stimulation of their common input pathway. Using whole cell patch clamp recordings in ferret thalamic slices, we compared single excitatory postsynaptic current decay kinetics, presynaptic glutamate release dynamics through paired pulse facilitation and responses to corticothalamic train stimulation. We found that single thalamic reticular nucleus excitatory postsynaptic currents were significantly sharper than lateral geniculate nucleus responses. The mean thalamic reticular nucleus excitatory postsynaptic current decay constant (tau) was 4.9+/-0.5 ms, while the mean lateral geniculate nucleus excitatory postsynaptic current tau value was 11.8+/-0.8 ms. Presynaptic release dynamics as measured by responses to paired stimuli were conserved between the thalamic reticular nucleus and lateral geniculate nucleus. However, facilitating responses to train stimulation were markedly different between nuclei. Lateral geniculate nucleus responses showed proportionately larger facilitation (reaching 842.9 +/- 76.4% of excitatory postsynaptic current 1 amplitude) than thalamic reticular nucleus responses (reaching 223.1 +/- 44.0% of excitatory postsynaptic current 1 amplitude). These data indicate that while the corticothalamic pathway produces excitatory postsynaptic currents in both the thalamic reticular nucleus and lateral geniculate nucleus, other factors uniquely affect the functional integration of the inputs in each nucleus.     

Transient direct connection of vestibular mossy fibers to the vestibulocerebellar Purkinje cells in early postnatal development of kittens

Postnatal development of mossy fiber afferents from the vestibular and the visual system to the vestibulocerebellum was studied electrophysiologically and morphologically. In kittens anesthetized with pentobarbital sodium and N2O plus halothane, extracellular simple and complex spikes of Purkinje cells were recorded in the flocculus, nodulus and uvula. In the flocculus, stimulation of the VIIIth, but not the optic nerve, evoked simple spike responses with a latency of 16 ms at the day of birth which decreased to 5 ms by day 15 (short latency group). On the other hand, another group of simple spike responses with much longer latencies (50-80 ms) began to be elicited on day 7 via both the optic and VIIIth nerves. The latency decreased to 24 ms by day 15 and 10 ms on day 30. These latencies further shortened with development to the adult latency value (3-5 ms). Simple spike responses of the short latency group were also evoked in the nodulus and uvula from the VIIIth nerve with a slightly longer latency than that in the flocculus (23 ms on day 3 and 12 ms on day 17). Because of the immaturity of granule cells in early postnatal days, short latency simple spike responses from the VIIIth nerve suggested the direct synaptic connection of vestibular mossy fibers with Purkinje cells. Horseradish peroxidase was injected into the white matter of the flocculus, nodulus and uvula in slice preparations. Mossy fibers labeled with horseradish peroxidase showed fine branches extending to reach Purkinje cell somata from mossy swellings in the internal granular layer during days 2-20. Electron microscopy showed that the labeled mossy fibers made intimate contacts with Purkinje cell somata and the terminals contained many round synaptic vesicles. Pre and postsynaptic densities were occasionally found. After day 20, direct mossy fiber connections with Purkinje cells could not be observed. During days 7-20, these direct connections, as well as mossy fiber-granule cell connections could be observed. It was demonstrated that during early postnatal development, vestibular mossy fibers temporarily make direct contact with Purkinje cells, through which impulses could be transmitted to elicit simple spikes in Purkinje cells.     

Temporal characteristics of tactile stimuli influence the response profile of cerebellar Golgi cells

An increasing number of studies have investigated the effect of stimulation parameters on neuronal response properties. Here, we describe the effect of temporal characteristics of tactile stimuli, more specifically the stimulation frequency and duration, on the response profile of simultaneously recorded cerebellar and cerebral cortical units in ketamine–xylazine anaesthetized rats. Long stimulus durations (>50 ms) elicited ON and OFF excitatory components in response to the stimulus onset and offset respectively, in both the cortex and the cerebellum. Golgi cells responded on average 7.5 ms later to the stimulus withdrawal than to the stimulus onset. Furthermore, the corticopontine OFF responses in the cerebellum and OFF responses in the cortex showed congruent latency decreases and amplitude increases for longer stimulus durations (50–200 ms). Decreasing the stimulus frequency similarly affected the latency and amplitude of the responses for inter-stimuli intervals shorter than 200 ms. In view of these results, we speculate that the stimulus offset is regarded as a novel input, because both paradigms resulted in similar response amplitude and latency modifications. Finally, the results suggest that a 100–200 ms time window can be of particular importance for cerebellar processing of information in the somatosensory system.     

Differences in responses to 70 dB clicks of cerebellar units with simple versus complex spike activity: (i) In medial and lateral ansiform lobes and flocculus; and (ii) Before and after conditioning blink conditioned responses with clicks as conditioned stimuli

Activity was recorded from 554 cerebellar units in eleven conscious cats to determine if responses to 70 dB clicks differed in units with simple and complex spike discharges. Effects of region of recording and behavioral state (with click used as a conditioned stimulus for conditioning) were also assessed. Cells with only simple spikes were distinguished from cells that had the following types of complex spike events: Type I—simple or initial spike followed >1 ms by multiple spikes with baseline displacement (classical complex spikes), Type II—followed ≤1 ms by spikes with or without baseline displacement (spikes in the absolute refractory period should arise from a separate site of initiation), and Type III—followed by spikes and displacement too close to the baseline noise to distinguish as Type I or II. Among the groups mean baseline activity was greatest in cells with Type I complex spikes, least in cells with Type III complex spikes, and greater in Type II cells than simple cells. Significant increases in activity within 32 ms of presenting clicks were found in the groups of Type II cells and simple cells. These appear to be the main auditory responsive cells of the cerebellar regions studied. Activity of Type II cells best reflected the temporal properties of the click; responses of simple cells had slower onsets (except in flocculus) and longer durations. Responses to click in Type II and simple cells differed in recordings from: (i) lateral ansiform lobe (lateral crus I and portions of crus II), (ii) medial ansiform lobe (medial crus I), and (iii) flocculus. The largest mean responses above baseline in the first 32 ms after click were found in Type II cells of the lateral ansiform lobe with onsets of 8–16 ms. Magnitudes of response differed before and after conditioning and backward conditioning. In the lateral ansiform lobe, the <32 ms response to click was greater in Type II than simple cells in each state, but showed a greater increase above baseline after backward conditioning when conditioned responses were not produced than after conditioning. The onset of increased activity to click conditioned stimuli in Type II cells of the lateral ansiform region preceded the onset of the blink conditioned response after conditioning, consisted almost entirely of simple spikes, and reflected an increase in magnitude of response as opposed to an increased number of responsive units. After conditioning, an increased number of units in the flocculus responded to click conditioned stimuli in the 16–24 ms post stimulus period. Of the 16 cells with an onset of increased activity at this time, eight showed only simple spike activity. Seven of the remaining eight cells (all Type II) showed a significant increase in conditioned stimulus-evoked complex spiking above the low (usually <1/s) baseline level of complex spike discharges.

The findings support the conclusions that cerebellar units can respond rapidly enough to acoustic stimuli to play a role in auditory as well as motor processing and that the responses to 70 dB clicks differ among cells with simple and complex spike discharges. The differences are influenced substantially by the region of cerebellar recording and the behavioral state. The findings in cells of the flocculus offer the first evidence that complex as well as simple spike activity can contribute to an increased probability of discharge to click as a conditioned stimulus after conditioning.     

Potentiation of neuronal responses to natural visual input paired with postsynaptic activation in the hippocampus of the awake monkey.

Extracellular recordings were made in the hippocampal formation while the monkey performed a simple visual discrimination task in which the stimuli consisted of coloured patterns presented serially. By using this natural visual input to single hippocampal neurones, and experimentally pairing one of the stimuli with postsynaptic excitation induced by iontophoretically applied L-glutamate, we demonstrate that selective synaptic potentiation can result. Seven of 29 neurones tested showed potentiation. The potentiation was selective in that enhanced responses only occurred to the previously paired stimulus, and not to other visual stimuli. The potentiation was observed in CA3 neurones and lasted approximately 15 min. In each case the latency of the potentiated response occurred at 160 ms following the onset time of the stimulus.     

The influence of single VB thalamocortical impulses on barrel columns of rabbit somatosensory cortex

Extracellular recordings were obtained from single neurons in ventrobasal (VB) thalamus of awake rabbits while field potentials were recorded at various depths within topographically aligned and nonaligned barrel columns of somatosensory cortex (S1). Spike-triggered averages of cortical field potentials were obtained following action potentials in thalamic neurons. Action potentials in a VB neuron elicited a cortical response within layer 4 with three distinct components. 1) A biphasic, initially positive response (latency <1 ms) was interpreted to reflect activation of the VB axon terminals (the AxTP). This response was not affected by infusion of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist within the barrel. In contrast, later components of the response were completely eliminated and were interpreted to reflect focal synaptic potentials. 2) A negative potential [focal synaptic negativity (FSN)] occurred at a mean latency of 1.65 ms and lasted approximately 4 ms. This response had a rapid rise time ( approximately 0.7 ms) and was interpreted to reflect monosynaptic excitation. 3) The third component was a positive potential (the FSP), with a slow rise time and a half-amplitude duration of approximately 30 ms. The FSP showed a weak reversal in superficial cortical layers and was interpreted to reflect di/polysynaptic inhibition. The amplitudes of the AxTP, the FSN, and the FSP reached a peak near layer 4 and were highly attenuated in both superficial and deep cortical layers. All components were attenuated or absent when the cortical electrode was missaligned from the thalamic electrode by a single cortical barrel. Deconvolution procedures revealed that the autocorrelogram of the presynaptic VB neuron had very little influence on either the amplitude or duration of the AxTP or the FSN, and only a minor influence (mean, 11%) on the amplitude of the FSP. We conclude that individual VB thalamic impulses entering a cortical barrel engage both monosynaptic excitatory and di/polysynaptic inhibitory mechanisms. Putative inhibitory interneurons of an S1 barrel receive a highly divergent/convergent monosynaptic input from the topographically aligned VB barreloid, and this results in sharp synchrony among these interneurons. We suggest that single-fiber access to disynaptic inhibition is facilitated by this sharp synchrony, and that the FSP reflects a consequent synchronous wave of feed-forward inhibition within the S1 barrel.     

REORGANIZATION OF BARREL CIRCUITS LEADS TO THALAMICALLY-EVOKED CORTICAL EPILEPTIFORM ACTIVITY

We studied circuit activities in layer IV of rat somatosensory barrel cortex containing microgyri induced by neonatal freeze lesions. Structural abnormalities in GABAergic interneurons are present in the epileptogenic paramicrogyral area (PMG) and we therefore tested the hypothesis that decreased postsynaptic inhibition within barrel microcircuits occurs in the PMG and contributes to epileptogenesis when thalamocortical afferents are activated. In thalamocortical (TC) slices from na?ve animals, single electrical stimuli within the thalamic ventrobasal (VB) nucleus evoked transient cortical multi-unit activity lasting 65±42 ms. Similar stimuli in TC slices from lesioned barrel cortex elicited prolonged 850 ±100 ms paroxysmal discharges that originated in the PMG and propagated laterally over several mm. Paroxysmal discharges were shortened in duration by ~70 % when APV was applied, and were totally abolished by CNQX. The cortical paroxysmal discharges did not evoke thalamic oscillations. Whole cell patch clamp recordings showed that there was a shift in the balance of TC evoked responses in the PMG that favored excitation over inhibition. Dual whole-cell recordings in layer IV of the PMG indicated that there was selective loss of inhibition from fast-spiking interneurons to spiny neurons in the barrel circuits that likely contributed to unconstrained cortical recurrent excitation with generation and spread of paroxysmal discharges.     

Functional connections of the rat medial cortex and basal forebrain: an in vivo intracellular study.

Projections between the medial cortex and basal forebrain in the rat were demonstrated by intracellular recordings and the anterograde tracer Phaseolus vulgaris leucoagglutinin. Direct projections between these areas were indicated by antidromic action potentials, short latency (less than 5 ms) orthodromic potentials, and labeled axon terminals in the basal forebrain subsequent to iontophoresis of Phaseolus vulgaris leucoagglutinin into posterior cingulate cortex. High proportions of antidromic action potentials were encountered in responsive cortical neurons (66%) and basal forebrain neurons (97%). Antidromic latencies recorded in the basal forebrain (less than 1.0 ms) revealed fast ascending projections; cortical neurons showed both fast and slow descending projections (latencies of 0.3-3.7 ms). Relatively few synaptic potentials (none in the diagonal band of Broca) and sparse labeling of axon terminals observed in the basal forebrain indicated that the ascending projections may be the more physiologically important or, at least, densest pathway. Polysynaptic feedforward pathways were suggested through long latency (greater than 20 ms) inhibitory and excitatory postsynaptic potentials, the former being the more common response. Candidate inhibitory neurons were identified in both cortex and basal forebrain. Possible monosynaptic (less than 5 ms) inhibitory postsynaptic and antidromic responses in these cells provided evidence that candidate inhibitory neurons participate in the reciprocal pathways.     

Suprachiasmatic nucleus communicates with anterior thalamic paraventricular nucleus neurons via rapid glutamatergic and gabaergic neurotransmission: state-dependent response patterns observed in vitro

The hypothalamic suprachiasmatic nucleus uniquely projects to the midline thalamic paraventricular nucleus. To characterize this projection, patch clamp techniques applied in acute rat brain slice preparations examined responses of anterior thalamic paraventricular nucleus neurons to focal suprachiasmatic nucleus stimulation. Whole cell recordings from slices obtained during daytime (n=40) revealed neurons with a mean membrane potential of -66+/-1.2 mV, input conductance of 1.5+/-0.1 nS and state-dependent tonic or burst firing patterns. Electrical stimulation (one or four pulses) in suprachiasmatic nucleus elicited monosynaptic excitatory postsynaptic potentials (mean latency of 12.6+/-0.6 ms; n=12), featuring both AMPA and N-methyl-D-aspartate-glutamate receptor-mediated components, and monosynaptic bicuculline-sensitive inhibitory postsynaptic potentials (mean latency of 16.6+/-0.6 ms; n=7) reversing polarity at -72+/-2.6 mV, close to the chloride equilibrium potential. Glutamate microstimulation of suprachiasmatic nucleus also elicited transient increases in spontaneous excitatory or inhibitory postsynaptic currents in anterior thalamic paraventricular neurons. Recordings from rats under reverse light/dark conditions (n=22) yielded essentially similar responses to electrical stimulation. At depolarized membrane potentials, suprachiasmatic nucleus-evoked excitatory postsynaptic potentials triggered single action potentials, while evoked inhibitory postsynaptic potentials elicited a silent period in ongoing tonic firing. By contrast, after manual adjustment of membrane potentials to hyperpolarized levels, neuronal response to the same "excitatory" stimulus was a low threshold spike and superimposed burst firing, while responses to "inhibitory" stimuli paradoxically elicited excitatory rebound low threshold spikes and burst firing. These data support the existence of glutamatergic and GABAergic efferents from the suprachiasmatic nucleus to its target neurons. Additionally, in thalamic paraventricular nucleus neurons, responses to activation of their suprachiasmatic afferents may vary in accordance with their membrane potential-dependent intrinsic properties, a characteristic typical of thalamocortical neurons.     

Comparative study on the offset responses of simple cells and complex cells in the primary visual cortex of the cat

Simple and complex cells are two basic and distinct functional types of neurons in the mammalian primary visual cortex. Here, we studied the onset response and the offset response of simple and complex cells to a flashing visual stimulus in the cat's area 17. Compared with simple cells, complex cells exhibited greater similarity between the onset and offset responses in peak latency. For simple cells, onset response had greater peak amplitude and signal-to-noise ratio than offset response, and for complex cells, vice versa. For both types of cortical cells, the amplitude of offset responses increased with stimulus duration within 100 ms significantly, while the onset response did not. However, to elicit a detectable offset response, complex cells tended to require shorter stimulus duration than simple cells did. In regard to the similarity of psychophysical data, these results suggest that the rebound offset response of cortical cells to disappearance of a visual pattern might be correlated to visual persistence in humans.     

Synaptic properties of thalamic and intracortical inputs to layer 4 of the first- and higher-order cortical areas in the auditory and somatosensory systems

The thalamus is an essential structure in the mammalian forebrain conveying information topographically from the sensory periphery to primary neocortical areas. Beyond this initial processing stage, "higher-order" thalamocortical connections have been presumed to serve only a modulatory role, or are otherwise functionally disregarded. Here we demonstrate that these "higher-order" thalamic nuclei share similar synaptic properties with the "first-order" thalamic nuclei. Using whole cell recordings from layer 4 neurons in thalamocortical slice preparations in the mouse somatosensory and auditory systems, we found that electrical stimulation in all thalamic nuclei elicited large, glutamatergic excitatory postsynaptic potentials (EPSPs) that depress in response to repetitive stimulation and that fail to activate a metabotropic glutamate response. In contrast, the intracortical inputs from layer 6 to layer 4 exhibit facilitating EPSPs. These data suggest that higher-order thalamocortical projections may serve a functional role similar to the first-order nuclei, whereas both are physiologically distinct from the intracortical layer 6 inputs. These results suggest an alternate route for information transfer between cortical areas via a corticothalamocortical pathway.     

Sub- and suprathreshold receptive field properties of pyramidal neurones in layers 5A and 5B of rat somatosensory barrel cortex

Layer 5 (L5) pyramidal neurones constitute a major sub- and intracortical output of the somatosensory cortex. This layer 5 is segregated into layers 5A and 5B which receive and distribute relatively independent afferent and efferent pathways. We performed in vivo whole-cell recordings from L5 neurones of the somatosensory (barrel) cortex of urethane-anaesthetized rats (aged 27–31 days). By delivering 6 deg single whisker deflections, whisker pad receptive fields were mapped for 16 L5A and 11 L5B neurones located below the layer 4 whisker-barrels. Average resting membrane potentials were −75.6 ± 1.1 mV, and spontaneous action potential (AP) rates were 0.54 ± 0.14 APs s⁻¹. Principal whisker (PW) evoked responses were similar in L5A and L5B neurones, with an average 5.0 ± 0.6 mV postsynaptic potential (PSP) and 0.12 ± 0.03 APs per stimulus. The layer 5A sub- and suprathreshold receptive fields (RFs) were more confined to the principle whisker than those of layer 5B. The basal dendritic arbors of layer 5A and 5B cells were located below both layer 4 barrels and septa, and the cell bodies were biased towards the barrel walls. Responses in both L5A and L5B developed slowly, with onset latencies of 10.1 ± 0.5 ms and peak latencies of 33.9 ± 3.3 ms. Contralateral multi-whisker stimulation evoked PSPs similar in amplitude to those of PW deflections; whereas, ipsilateral stimulation evoked smaller and longer latency PSPs. We conclude that in L5 a whisker deflection is represented in two ways: focally by L5A pyramids and more diffusely by L5B pyramids as a result of combining different inputs from lemniscal and paralemniscal pathways. The relevant output evoked by a whisker deflection could be the ensemble activity in the anatomically defined cortical modules associated with a single or a few barrel-columns.     

Strong, reliable and precise synaptic connections between thalamic relay cells and neurones of the nucleus reticularis in juvenile rats

The thalamic reticular nucleus (nRT) is composed entirely of GABAergic inhibitory neurones that receive input from pyramidal cortical neurones and excitatory relay cells of the ventrobasal complex of the thalamus (VB). It plays a major role in the synchrony of thalamic networks, yet the synaptic connections it receives from VB cells have never been fully physiologically characterised. Here, whole-cell current-clamp recordings were obtained from 22 synaptically connected VB-nRT cell pairs in slices of juvenile (P14-20) rats. At 34-36 °C, single presynaptic APs evoked unitary EPSPs in nRT cells with a peak amplitude of 7.4 ± 1.5 mV (mean ± s.e.m .) and a decay time constant of 15.1 ± 0.9 ms. Only four out of 22 pairs showed transmission failures at a mean rate of 6.8 ± 1.1 %. An NMDA receptor (NMDAR)-mediated component was significant at rest and subsequent EPSPs in a train were depressed. Only one out of 14 pairs tested was reciprocally connected; the observed IPSPs in the VB cell had a peak amplitude of 0.8 mV and were completely abolished in the presence of 10 μ m bicuculline. Thus, synaptic connections from VB cells to nRT neurones are mainly 'drivers', while a small subset of cells form closed disynaptic loops.     

Synaptic responsiveness of neocortical neurons to callosal volleys during paroxysmal depolarizing shifts

Based on intracellular recordings in vivo, we investigated the responsiveness of cat neocortical neurons to callosal volleys during different phases of spontaneously occurring or electrically induced electrographic seizures, compared with control periods of slow sleep-like oscillations. Overt seizures, with spiking, triggered by pulse-trains to the callosal pathway, started with a latency of approximately 20 s after cessation of stimulation, thus contrasting with paroxysmal activity elicited by ipsilateral cortical or thalamic stimulation that is initiated immediately after electrical stimulation. During the rather long preparatory period to callosally triggered seizures, cortical neurons displayed subthreshold depolarizing runs at 4-7 Hz, associated with increased amplitudes of excitatory postsynaptic potentials. The sequential analysis of neuronal responsiveness during different components of spike-wave complexes revealed progressively increased amplitudes of callosally evoked postsynaptic excitatory responses in regular-spiking and fast-rhythmic-bursting neurons, over a period of approximately 20 ms prior to the generation of paroxysmal depolarizing shifts. These data support the concept that seizures consisting of spike-wave complexes originate within the neocortex through a progressive synaptic buildup and that their synchronization is achieved, at least partially, by cortical commissural synaptic linkages.     

Intracortical circuits in rat anterior cingulate cortex are activated by nociceptive inputs mediated by medial thalamus

We investigated the afferents and intracortical synaptic organization of the anterior cingulate cortex (ACC) during noxious electrical stimulation. Extracellular field potentials were recorded simultaneously from 16 electrodes spanning all layers of the ACC in male Sprague-Dawley rats anesthetized by halothane inhalation. Laminar-specific transmembrane currents were calculated with the current source density analysis method. Two major groups of evoked sink currents were identified: an early group (latency = 54.04 +/- 2.12 ms; 0.63 +/- 0.07 mV/mm(2)) in layers V-VI and a more intense late group (latency = 80.07 +/- 4.85 ms; 2.16 +/- 0.22 mV/mm(2)) in layer II/III and layer V. Multiunit activities were evoked mainly in layer V and deep layer II/III with latencies similar to that of the early and late sink groups. The evoked EPSP latencies of pyramidal neurons in layers II/III and V related closely with the sink currents. The sink currents were inhibited by intracortical injection of CNQX (1 mM, 1 microl), a glutaminergic receptor antagonist, and enhanced by intraperitoneal (5 mg/kg) and intracortical (10 microg/microl, 1 microl) injection of morphine, a mu-opioid receptor agonist. Paired-pulse depression was observed with interpulse intervals of 50 to 1,000 ms. High-frequency stimulation (100 Hz, 11 pulses) enhanced evoked responses in the ACC and evoked medial thalamic (MT) unit activities. MT lesions blocked evoked responses in the ACC. Our results demonstrated that two distinct synaptic circuits in the ACC were activated by noxious stimuli and that the MT is the major thalamic relay that transmits nociceptive information to the ACC.     

Synaptic potentials evoked in spiny neurons in rat neostriatal grafts by cortical and thalamic stimulation.

1. Fetal rat striatal primordia were implanted into the neostriatum of adult rats 2 days after kainic acid lesion. Two to 6 mo after transplantation, in vivo intracellular recording and staining were performed to study the responses of spiny neurons in the grafts to the cortical and thalamic stimuli. The physiological characteristics and synaptic responses of 27 cells recorded in the grafts were compared with a sample of 23 neurons recorded from the surrounding host neostriatum in the same animals. Nineteen of the graft neurons and 19 of the host neurons were identified as spiny neurons by intracellular staining with biocytin. The responses of the remaining neurons were the same as those of identified spiny cells. 2. The spontaneous synaptically driven membrane potential shifts and long-lasting responses to afferent stimulation that are characteristic of neostriatal cells in normal animals were greatly reduced or absent in graft neurons. Presumably this reflects the reduction in synaptic input to the grafts and the lack of convergence of inputs from diverse sources. 3. Short-latency synaptic responses to cortical and thalamic stimulation were present and could consist of either excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs). The IPSPs were accompanied by a membrane conductance increase, and their reversal potentials could be altered by injection of chloride ions. Several minutes after impaling the cell, the IPSPs gradually disappeared, and the same stimuli could then evoke EPSPs. The disappearance of the IPSPs was independent of the presence of chloride in the electrodes. Most of the EPSP responses appeared to be monosynaptic but occurred at longer latencies than those seen in host neurons of the same type. 4. In cells not exhibiting IPSPs, or after the IPSP responses disappeared, cortical or thalamic stimulation could evoke slow depolarizing potentials and bursts of action potentials. These could not be evoked by current injection. They could be prevented or delayed by an exaggerated action potential after hyperpolarization that developed in neurons maintained in a depolarized state for several seconds, but could not be prevented by passage of hyperpolarizing current from the recording electrode. 5. The input resistance of graft spiny neurons was higher than that of the host cells, and time constants were longer. Both of these properties appeared to be due to the absence of the strong inward rectification that is usually present at resting membrane potentials in neostriatal neurons.     

Neuronal responses from beyond the classic receptive field in V1 of alert monkeys

Responses of primary visual cortex (V1) neurons to stimuli inside the classic receptive field (CRF) can be modulated by stimuli outside the CRF. We recently reported that responses of most V1 neurons to a line in the CRF center are inhibited by large surround-stimuli and that this modulation is stimulus selective. Here we report that a significant proportion of V1 neurons in alert monkeys respond directly to stimuli outside the CRF with very long latency and much reduced selectivity. When surround stimuli are presented alone, three response patterns can be distinguished in 153 single- or multiunits tested: (1) 31.4% have no significant response; (2) 50.3% show excitatory responses that are significantly higher than spontaneous activity. The average latency of these responses is about 145 ms, 2–3 times longer than center responses; (3) 18.3% show suppressed spontaneous activity after stimulus onset. The direct surround responses are found to be only weakly selective for the orientation of contextual lines, and not selective for other contextual patterns tested. While the outburst of responses to stimuli within the CRF is not affected by reducing stimulus duration from 500 ms to 50 ms, late excitatory surround responses are virtually eliminated. We propose that the late excitatory surround responses to extra-CRF stimulation alone are the reflection of feedback from higher cortical areas and may contribute to reduced contextual inhibition of cells in V1. This could play a role in figure-ground segregation. Electronic Publication     

Evidence of input from lagged cells in the lateral geniculate nucleus to simple cells in cortical area 17 of the cat.

1. The visual cortex receives several types of afferents from the lateral geniculate nucleus (LGN) of the thalamus. In the cat, previous work studied the ON/OFF and X/Y distinctions, investigating their convergence and segregation in cortex. Here we pursue the lagged/nonlagged dichotomy as it applies to simple cells in area 17. Lagged and nonlagged cells in the A-layers of the LGN can be distinguished by the timing of their responses to sinusoidally luminance-modulated stimuli. We therefore used similar stimuli in cortex to search for signs of lagged and nonlagged inputs to cortical cells. 2. Line-weighting functions were obtained from 37 simple cells. A bar was presented at a series of positions across the receptive field, with the luminance of the bar modulated sinusoidally at a series of temporal frequencies. First harmonic response amplitude and phase values for each position were plotted as a function of temporal frequency. Linear regression on the phase versus temporal frequency data provided estimates of latency (slope) and absolute phase (intercept) for each receptive-field position tested. These two parameters were previously shown to distinguish between lagged and nonlagged LGN cells. Lagged cells generally have latencies > 100 ms and absolute phase lags; nonlagged cells have latencies < 100 ms and absolute phase leads. With the use of these criteria, we classified responses at discrete positions inside cortical receptive fields as lagged-like and nonlagged-like. 3. Both lagged-like and nonlagged-like responses were observed. The majority of cortical cells had only or nearly only nonlagged-like zones. In 15 of the 37 cells, however, the receptive field consisted of > or = 20% lagged-like zones. For eight of these cells, lagged-like responses predominated. 4. The distribution of latency and absolute phase across the sample of cortical simple cell receptive fields resembled the distribution for LGN cells. The resemblance was especially striking when only cells in or adjacent to geniculate recipient layers were considered. Absolute phase lags were almost uniformly associated with long latencies. Absolute phase leads were generally associated with short latencies, although cortical cells responded with long latencies and absolute phase leads slightly more often than LGN cells. 5. Cells in which a high percentage of lagged-like responses were observed had a restricted laminar localization, with all but two being found in layer 4B or 5A. Cells with predominantly nonlagged-like responses were found in all layers. 6. Lagged-like zones can not be easily explained as a result of stimulating combinations of nonlagged inputs.(ABSTRACT TRUNCATED AT 400 WORDS)