Fast-spiking Cells Research Articles

Threshold firing frequency-current relationships of neurons in rat somatosensory cortex: type 1 and type 2 dynamics.

Neurons and dynamical models of spike generation display two different types of threshold behavior, with steady current stimulation: type 1 [the firing frequency vs. current (f-I) relationship is continuous at threshold) and type 2 (discontinuous f-I)]. The dynamics at threshold can have profound effects on the encoding of input as spikes, the sensitivity of spike generation to input noise, and the coherence of population firing. We have examined the f-I and frequency-conductance (f-g) relationships of cells in layer 2/3 of slices of young (15-21 DIV) rat somatosensory cortex, focusing in detail on the nature of the threshold. Using white-noise stimulation, we also measured firing frequency and interspike interval variability as a function of noise amplitude. Regular-spiking (RS) pyramidal neurons show a type 1 threshold, consistent with their well-known ability to fire regularly at very low frequencies. In fast-spiking (FS) inhibitory interneurons, although regular firing is supported over a wide range of frequencies, there is a clear discontinuity in their f-I relationship at threshold (type 2), which has not previously been highlighted. FS neurons are unable to support maintained periodic firing below a critical frequency fc, in the range of 10 to 30 Hz. Very close to threshold, FS cells switch irregularly between bursts of periodic firing and subthreshold oscillations. These characteristics mean that the dynamics of RS neurons are well suited to encoding inputs into low-frequency firing rates, whereas the dynamics of FS neurons are suited to maintaining and quickly synchronizing to gamma and higher-frequency input.

Major Differences in Inhibitory Synaptic Transmission onto Two Neocortical Interneuron Subclasses

Locally projecting GABAergic interneurons are the major providers of inhibition in the neocortex and play a crucial role in several brain functions. Neocortical interneurons are connected via electrical and chemical synapses that may be crucial in modulating complex network oscillations. We investigated the properties of spontaneous and evoked IPSCs in two morphologically and physiologically identified interneuron subtypes, the fast-spiking (FS) and low threshold-spiking (LTS) cells in layer V of rodent sensorimotor cortex. We found that IPSCs recorded in FS cells were several orders of magnitude more frequent, larger in amplitude, and had faster kinetics than IPSCs recorded in LTS cells. GABA(A) receptor alpha- and beta-subunit selective modulators, zolpidem and loreclezole, had different effects on IPSCs in FS and LTS interneurons, suggesting differential expression of GABA(A) receptor subunit subtypes. These pharmacological data indicated that the alpha1 subunit subtype is poorly expressed by LTS cells but makes a large contribution to GABA(A) receptors on FS cells. This was confirmed by experiments performed in genetically modified mice in which the alpha1 subunit had been made insensitive to benzodiazepine-like agonists. These results suggest that differences in IPSC waveform are likely attributable to distinctive expression of GABA(A) receptor subunits in FS and LTS cells. The particular properties of GABAergic input on different interneuronal subtypes might have important consequences for generation and pacing of cortical rhythms underlying several brain functions. Moreover, selective pharmacological manipulation of distinct inhibitory circuits might allow regulation of pyramidal cell activities under specific physiological and pathophysiological conditions.

Electrical Synapses and Synchrony: The Role of Intrinsic Currents

Electrical synapses are ubiquitous in the mammalian CNS. Particularly in the neocortex, electrical synapses have been shown to connect low-threshold spiking (LTS) as well as fast spiking (FS) interneurons. Experiments have highlighted the roles of electrical synapses in the dynamics of neuronal networks. Here we investigate theoretically how intrinsic cell properties affect the synchronization of neurons interacting by electrical synapses. Numerical simulations of a network of conductance-based neurons randomly connected with electrical synapses show that potassium currents promote synchrony, whereas the persistent sodium current impedes it. Furthermore, synchrony varies with the firing rate in qualitatively different ways depending on the intrinsic currents. We also study analytically a network of quadratic integrate-and-fire neurons. We relate the stability of the asynchronous state of this network to the phase-response function (PRF), which characterizes the effect of small perturbations on the firing timing of the neurons. In particular, we show that the greater the skew of the PRF toward the first half of the period, the more stable the asynchronous state. Combining our simulations with our analytical results, we establish general rules to predict the dynamic state of large networks of neurons coupled with electrical synapses. Our work provides a natural explanation for surprising experimental observations that blocking electrical synapses may increase the synchrony of neuronal activity. It also suggests different synchronization properties for LTS and FS cells. Finally, we propose to further test our predictions in experiments using dynamic clamp techniques.

Heterogeneous actions of serotonin on interneurons in rat visual cortex.

The effects of serotonin (5-HT) on excitability of two cortical interneuronal subtypes, fast-spiking (FS) and low threshold spike (LTS) cells, and on spontaneous inhibitory postsynaptic currents (sIPSCs) in layer V pyramidal cells were studied in rat visual cortical slices using whole-cell recording techniques. Twenty-two of 28 FS and 26 of 35 LTS interneurons responded to local application of 5-HT. In the group of responsive neurons, 5-HT elicited an inward current in 50% of FS cells and 15% of LTS cells, an outward current was evoked in 41% of FS cells and 81% of LTS cells, and an inward current followed by an outward current in 9% of FS cells and 4% LTS cells. The inward and outward currents were blocked by a 5-HT(3) receptor antagonist, tropisetron, and a 5-HT(1A) receptor antagonist, NAN-190, respectively. The 5-HT-induced inward and outward currents were both associated with an increase in membrane conductance. The estimated reversal potential was more positive than -40 mV for the inward current and close to the calculated K(+) equilibrium potential for the outward current. The 5-HT application caused an increase, a decrease, or an increase followed by a decrease in the frequency of sIPSCs in pyramidal cells. The 5-HT(3) receptor agonist 1-(m-chlorophenyl) biguanide increased the frequency of larger and fast-rising sIPSCs, whereas the 5-HT(1A) receptor agonist (+/-)8-hydroxydipropylaminotetralin hydrobromide elicited opposite effects and decreased the frequency of large events. These data indicate that serotonergic activation imposes complex actions on cortical inhibitory networks, which may lead to changes in cortical information processing.

Modulation of inhibitory autapses and synapses on rat CA1 interneurones by GABA(A) receptor ligands.

To determine whether autaptic inhibition plays a functional role in the adult hippocampus, the action potential afterhyperpolarisations (spike AHPs) of CA1 interneurones were investigated in 25 basket, three bistratified and eight axo-axonic cells. The spike AHPs showed two minima in all regular-spiking (5), burst-firing (3) and in many fast-spiking cells (17:28). The fast component had a time-to-peak (TTP) of 1.2 +/- 0.5 ms, the slower TTP was very variable (range of 3.3-103 ms). The AHP width at half-amplitude (HW) was 12.5 +/- 5.7 ms in fast-spiking, 29.3 +/- 18 ms in regular-spiking and 99.7 +/- 42 ms in burst-firing cells. Axo-axonic cells never establish autapses, and the fast-spiking variety showed narrow (HW: 3.9 +/- 0.7 ms) spike AHPs with only one AHP minimum (TTP: 0.9 +/- 0.1 ms). When challenged with GABA(A) receptor modulators, spike AHPs in basket and bistratified cells were enhanced by zolpidem (HW by 18.4 +/- 6.2 % in 10:15 cells tested), diazepam (45.2 +/- 0.5 %, 6:7), etomidate (43.9 +/- 36 %, 6:8) and pentobarbitone sodium (41 %, 1:1), and were depressed by bicuculline (-41 +/- 5.7 %, 5:8) and picrotoxin (-54 %, 1:1), and the enhancement produced by zolpidem was reduced by flumazenil (-31 +/- 13 %, relative to the AHP HW during exposure to zolpidem, 3:4). Neuronal excitability was modulated in parallel. The spike AHPs of three axo-axonic cells tested showed no sensitivity to etomidate, pentobarbitone or diazepam. Interneurone-to-interneurone inhibitory postsynaptic potentials (IPSPs), studied with dual intracellular recordings, had time courses resembling those of the spike AHPs. The IPSP HW was 13.4 +/- 2.8 ms in fast-spiking (n = 16) and 28.7 +/- 5.8 ms in regular-spiking/burst-firing cells (n = 6), and the benzodiazepine1-selective modulator zolpidem strongly enhanced these IPSPs (45 +/- 28 %, n = 5). Interneurones with spike AHPs affected by the GABA(A) receptor ligands exhibited 3.8 +/- 1.9 close autaptic appositions. In three basket cells studied at the ultrastructural level 6 of 6, 1 of 2 and 1 of 2 close appositions were confirmed as autapses. Therefore, in the hippocampus autaptic connections contribute to spike AHPs in many interneurones. These autapses influence neuronal firing and responses to GABA(A) receptor ligands.

Electrophysiological and morphological diversity of neurons from the rat subicular complex in vitro.

We combined whole-cell recordings with Neurobiotin labeling to examine the electrophysiological and morphological properties of neurons from the ventral subicular complex in vitro (including the subicular, presubicular, and parasubicular areas). No a priori morphological sampling criteria were used to select cells. Cells were classified as bursting (IB), regular-spiking (RS), and fast-spiking (FS) according to their firing patterns in response to depolarizing current pulses. A number of cells remained unclassified. We found 54% RS, 26% IB, 11% FS, and 9% unclassified cells out of a total of 131 neurons examined. We also found cells showing intrinsic membrane potential oscillations (MPO) (6%), which represented a subgroup of the unclassified cells. We analyzed several electrophysiological parameters and found that RS and IB cells can be subclassified into two separate subgroups. RS cells were subclassified as tonic and adapting, according to the degree of firing adaptation. Both responded with single spikes to orthodromic stimulation. IB cells were subclassified in two subgroups according to their capacity to fire more than one burst, and showed different responses to orthodromic stimulation. We observed that bursting in these two subgroups appeared to involve both Ca2+ and persistent Na+ components. Both IB and RS cells, as well as MPO neurons, were projecting cells. FS cells were morphologically identified as local circuit interneurons. We also analyzed the spatial distribution of these cell types from the vicinity of CA1 to the parasubicular areas. We conclude that, in contrast to the commonly accepted idea of the subicular complex as a bursting structure, there is a wide electrophysiological variability even within a given cellular group.

Feedforward Mechanisms of Excitatory and Inhibitory Cortical Receptive Fields

Excitatory and inhibitory cortical layer IV neurons have distinctive response properties. Thalamocortical connectivity that may underlie differences was examined using cross-correlation analyses of pairs of thalamic and cortical neurons in the rat whisker/barrel system. Cortical layer IV cells discharging fast spikes, presumed inhibitory neurons, were distinguished from regular-spike units, presumed excitatory neurons, by the extracellular waveform shape. Regular-spike neurons fired less robustly and had smaller receptive fields (RFs) and greater directional tuning than fast-spike cells. Presumed excitatory neurons were less likely to receive thalamocortical connections, and their connections were, on average, weaker. RF properties of thalamic inputs to both cell types were equivalent, except that the most highly responsive thalamic cells contacted only fast-spike neurons. In contrast, the size and directional tuning of cortical RFs were related to the number of detectable thalamocortical inputs. Connected thalamocortical pairs were likely to have matching RF characteristics. The smaller, more directionally selective RFs of excitatory neurons may be a consequence of their weaker net thalamic drive, their more nonlinear firing characteristics and pervasive feedforward inhibition provided by strongly driven, broadly tuned inhibitory neurons.

Short-term dynamics of thalamocortical and intracortical synapses onto layer 6 neurons in neocortex.

Layer 6 is the main source of neocortical connections back to specific thalamic nuclei. Corticothalamic (CT) systems play an important role in shaping sensory input, but little is known about the functional circuitry that generates CT activity. We recorded from the two main types of neurons in layer 6, regular-spiking (RS; pyramidal neurons) and fast-spiking (FS; inhibitory interneurons) cells and compared the physiological properties of different excitatory inputs. Thalamic stimulation evoked two monosynaptic inputs with distinct properties: suspected thalamocortical (TC) synaptic events had short latencies, short-term synaptic depression, and paired-pulse responses that suggested subnormal axonal conduction. A second group of synaptic responses likely originated from intracortical collaterals of CT cells that were antidromically activated from the thalamus. These intracortical responses had longer latencies, short-term synaptic facilitation, and were transmitted by axons with supernormal conduction. Suspected TC inputs to FS cells had significantly larger amplitudes than those onto RS cells. Dual recordings from neighboring neurons in layer 6 revealed both facilitating and depressing synaptic connections; the depressing synapses were probably formed by layer 6 cells that do not project to the thalamus, and thus were not sampled by thalamic stimulation. We conclude that layer 6 neurons integrate a variety of inputs with distinct temporal dynamics that are determined by the presynaptic cell type.

Electrical and chemical synapses among parvalbumin fast-spiking GABAergic interneurons in adult mouse neocortex.

Networks of gamma-aminobutyric acid (GABA)ergic interneurons connected via electrical and chemical synapses are thought to play an important role in detecting and promoting synchronous activity in the cerebral cortex. Although the properties of electrical and chemical synaptic interactions among inhibitory interneurons are critical for their function as a network, they have only been studied systematically in juvenile animals. Here, we have used transgenic mice expressing the enhanced green fluorescent protein in cells containing parvalbumin (PV) to study the synaptic connectivity among fast-spiking (FS) cells in slices from adult animals (2-7 months old). We have recorded from pairs of PV-FS cells and found that the majority of them were electrically coupled (61%, 14 of 23 pairs). In addition, 78% of the pairs were connected via GABAergic chemical synapses, often reciprocally. The average coupling coefficient for step injections was 1.5% (n = 14), a smaller value than that reported in juvenile animals. GABA-mediated inhibitory postsynaptic currents and potentials decayed with exponential time constants of 2.6 and 5.9 ms, respectively, and exhibited paired-pulse depression (50-ms interval). The inhibitory synaptic responses in the adult were faster than those observed in young animals. Our results indicate that PV-FS cells are highly interconnected in the adult cerebral cortex by both electrical and chemical synapses, establishing networks that can have important implications for coordinating activity in cortical circuits.

Synaptic inhibition of pyramidal cells evoked by different interneuronal subtypes in layer v of rat visual cortex.

Properties of GABA(A) receptor-mediated unitary inhibitory postsynaptic currents (uIPSCs) in pyramidal (P) cells, evoked by fast spiking (FS) and low-threshold spike (LTS) subtypes of interneurons in layer V of rat visual cortex slices were examined using dual whole cell recordings. uIPSCs evoked by FS cells were larger and faster rising than those evoked by LTS cells, consistent with the known primary projections of FS and LTS cell axons to perisomatic and distal dendritic areas of layer V pyramidal cells, respectively, and the resulting electrotonic attenuation for LTS-P synaptic events. Unexpectedly, the decay time constants for LTS-P and FS-P uIPSCs were not significantly different. Modeling results were consistent with differences in the underlying GABA(A) receptor-mediated conductance at LTS-P and FS-P synapses. Paired-pulse depression (PPD), present at both synapses, was associated with an increase in failure rate and a decrease in coefficient of variation, indicating that presynaptic mechanisms were involved. Furthermore, the second and first uIPSC amplitudes during PPD were not inversely correlated, suggesting that PPD at both synapses is independent of previous release and might not result from depletion of the releasable pool of synaptic vesicles. Short, 20-Hz trains of action potentials in presynaptic interneurons evoked trains of uIPSCs with exponentially decreasing amplitudes at both FS-P and LTS-P synapses. FS-P uIPSC amplitudes declined more slowly than those of LTS-P uIPSCs. Thus FS and LTS cells, with their differences in firing properties, synaptic connectivity with layer V P cells, and short-term synaptic dynamics, might play distinct roles in regulating the input-output relationship of the P cells.

The spatial dimensions of electrically coupled networks of interneurons in the neocortex.

Inhibitory interneurons of the neocortex are electrically coupled to cells of the same type through gap junctions. We studied the spatial organization of two types of interneurons in the rat somatosensory cortex: fast-spiking (FS) parvalbumin-immunoreactive (PV+) cells, and low threshold-spiking (LTS) somatostatin-immunoreactive (SS+) cells. Paired recordings in layer 4 demonstrated that both the probability of coupling and the coupling coefficient drop steeply with intersomatic distance, reaching zero beyond 200 microm. The dendritic arbors of FS and LTS cells were reconstructed from electrophysiologically characterized, biocytin-filled cells; the two cell types had only minor differences in the number and span of their dendrites. However, there was a markedly higher density of PV+ cells than SS+ cells. PV+ cells were densest in layer 4, while SS+ cell density peaked in the subgranular layers. From these data we estimate that there is measurable electrical coupling (directly or indirectly via intermediary cells) between each interneuron and 20-50 others. The large number of electrical synapses implies that each interneuron participates in a large, continuous syncytium. To evaluate the functional significance of these findings, we examined several simple architectures of coupled networks analytically. We present a mathematical method to estimate the average summated coupling conductance that each cell receives from all of its neighbors, and the average leak conductance of individual cells, and we suggest that these have the same order of magnitude. These quantitative results have important implications for the effects of electrical coupling on the dynamic behavior of interneuron networks.

The Spatial Dimensions of Electrically Coupled Networks of Interneurons in the Neocortex

Inhibitory interneurons of the neocortex are electrically coupled to cells of the same type through gap junctions. We studied the spatial organization of two types of interneurons in the rat somatosensory cortex: fast-spiking (FS) parvalbumin-immunoreactive (PV+) cells, and low threshold-spiking (LTS) somatostatin-immunoreactive (SS+) cells. Paired recordings in layer 4 demonstrated that both the probability of coupling and the coupling coefficient drop steeply with intersomatic distance, reaching zero beyond 200 μm. The dendritic arbors of FS and LTS cells were reconstructed from electrophysiologically characterized, biocytin-filled cells; the two cell types had only minor differences in the number and span of their dendrites. However, there was a markedly higher density of PV+ cells than SS+ cells. PV+ cells were densest in layer 4, while SS+ cell density peaked in the subgranular layers. From these data we estimate that there is measurable electrical coupling (directly or indirectly via intermediary cells) between each interneuron and 20–50 others. The large number of electrical synapses implies that each interneuron participates in a large, continuous syncytium. To evaluate the functional significance of these findings, we examined several simple architectures of coupled networks analytically. We present a mathematical method to estimate the average summated coupling conductance that each cell receives from all of its neighbors, and the average leak conductance of individual cells, and we suggest that these have the same order of magnitude. These quantitative results have important implications for the effects of electrical coupling on the dynamic behavior of interneuron networks.

Physiological and morphological diversity of immunocytochemically defined parvalbumin- and cholecystokinin-positive interneurones in CA1 of the adult rat hippocampus.

To investigate the electrophysiological properties, synaptic connections, and anatomy of individual parvalbumin-immunoreactive (PV-IR) and cholecystokinin-immunoreactive (CCK-IR) interneurones in CA1, dual intracellular recordings using biocytin-filled microelectrodes in slices of adult rat hippocampus were combined with fluorescence labelling of PV- and CCK-containing cells. Of 36 PV-IR cells, 29 were basket cells, with most of their axonal arbours in the stratum pyramidale (SP). Six were bistratified cells with axons ramifying throughout stratum oriens (SO) and stratum radiatum (SR). One was a putative axo-axonic cell with an axonal arbour confined to half of the SP and a narrow adjacent region of the SO. Of 27 CCK-IR neurones, 13 were basket cells, with most of their axonal arbours in the SP, and included basket cells with somata in the SP (6), SO (3), and SR (2) and at the border between the stratum lacunosum-moleculare (SLM) and the SR (2). In addition, several dendrite-targeting cell classes expressed CCK-IR: 4 of 9 bistratified cells with axons ramifying in the SO and SR; all five Schaffer-associated cells whose axons ramified extensively in the SR; both cells classified as quadrilaminar because their axons ramified in the SO, SP, SR, and SLM; one SO-SO cell whose dendritic and axonal arbours were contained within the SO; and one perforant path-associated cell with axonal and dendritic arbours within the distal SR and SLM. The majority (31 of 36) of PV-IR neurones recorded were fast-spiking, and most fast-spiking cells tested (25 of 29 basket, 1 axo-axonic, and 5 of 6 bistratified cells) were PV-IR. However, 1 of 6 regular-spiking basket, 1 of 4 regular-spiking bistratified, and 3 of 5 burst-firing basket cells were also PV-IR. In contrast, the majority (17 of 27) of the CCK-IR neurones recorded were regular-spiking, 3 were burst-firing, and 7 were fast-spiking. These data confirm that the majority of PV-IR and CCK-IR axon terminals innervate proximal portions of CA1 pyramidal cells. Most PV-IR cells are fast-spiking, whereas most CCK-IR cells are regular-spiking. In both neurochemical classes basket cells predominate, but both groups included subpopulations of dendrite-targeting cells. Despite these similarities, the two populations exhibited very different somatic distributions, and each contained cellular morphologies not represented in the other.

Cell-type-specific GABA responses and chloride homeostasis in the cortex and amygdala.

The GABA responses of fast-spiking (FS) interneurons and regular-spiking (RS) principal cells were studied using whole cell and perforated-patch recordings in slices of the basolateral amygdala, neo-, and perirhinal cortex. In these three areas, responses to exogenous and synaptically released GABA were abolished by GABA(A) receptor antagonists in FS cells but also included a GABA(B) component in RS cells. Moreover, E(GABA(A)) of FS and RS cells differed from the calculated E(Cl) (-61 mV), but in opposite direction (FS, -54 mV; RS, -72 mV). This was not due to a differential dialysis of FS and RS cells by the pipette solution because the discrepancy persisted when recordings were obtained with the perforated-patch-clamp technique, using the cation-selective ionophore gramicidin. Moreover, pharmacological inhibition of cation-chloride cotransporters revealed that the differing E(GABA(A)) of FS and RS neurons arises from cell-type-specific chloride homeostatic mechanisms. Indeed, the prevalent regulators of the intracellular chloride concentration are cotransporters that accumulate chloride in FS cells and extrude chloride in RS neurons. Thus, our results suggest that in the basolateral amygdala as well as in the parietal and perirhinal cortices, FS interneurons are more excitable than principal cells not only by virtue of their dissimilar electroresponsive properties but also because they express a different complement of GABA receptors and chloride homeostatic mechanisms.

Effect of the group I metabotropic glutamate agonist DHPG on the visual cortex.

Metabotropic glutamate receptors have a variety of effects in visual cortex that depend on the age of the animal, the layer of the cortex, and the group of the receptor. Here we describe these effects for group I receptors, using both in vivo and in vitro preparations. The metabotropic group I glutamate receptor agonist 3,5 dihydroxyphenylglycine (DHPG) potentiates the responses to N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in slices of rat visual cortex. It also increases, initially, the visual response in the cat visual cortex. Both these effects are largest at 3-4 wk of age and decline to insignificance by 10 wk of age. Both are also largest in lower layers of cortex, which explains why the facilitatory effects found with the general metabotropic glutamate agonist 1S,3R aminocyclopentane-1,3-dicarboxylic acid (ACPD) are observed only in lower layers. Prolonged application of DHPG in the cat visual cortex, after the initial excitatory effect, produces depression. We also found that DHPG facilitates the NMDA response in fast-spiking cells, which are inhibitory, providing a partial explanation for this. Thus there are multiple effects of group I metabotropic glutamate receptors, which vary with layer and age in visual cortex.

Focal synchronization of ripples (80-200 Hz) in neocortex and their neuronal correlates.

Field potentials from different neocortical areas and intracellular recordings from areas 5 and 7 in acutely prepared cats under ketamine-xylazine anesthesia and during natural states of vigilance in chronic experiments, revealed the presence of fast oscillations (80-200 Hz), termed ripples. During anesthesia and slow-wave sleep, these oscillations were selectively related to the depth-negative (depolarizing) component of the field slow oscillation (0.5-1 Hz) and could be synchronized over ~10 mm. The dependence of ripples on neuronal depolarization was also shown by their increased amplitude in field potentials in parallel with progressively more depolarized values of the membrane potential of neurons. The origin of ripples was intracortical as they were also detected in small isolated slabs from the suprasylvian gyrus. Of all types of electrophysiologically identified neocortical neurons, fast-rhythmic-bursting and fast-spiking cells displayed the highest firing rates during ripples. Although linked with neuronal excitation, ripples also comprised an important inhibitory component. Indeed, when regular-spiking neurons were recorded with chloride-filled pipettes, their firing rates increased and their phase relation with ripples was modified. Thus besides excitatory connections, inhibitory processes probably play a major role in the generation of ripples. During natural states of vigilance, ripples were generally more prominent during the depolarizing component of the slow oscillation in slow-wave sleep than during the states of waking and rapid-eye movement (REM) sleep. The mechanisms of generation and synchronization, and the possible functions of neocortical ripples in plasticity processes are discussed.

Distinct Firing Patterns of Neuronal Subtypes in Cortical Synchronized Activities

Cortical neurons, especially GABAergic interneurons, are composed of very diverse subtypes. It remains to be investigated whether each subtype shows a unique firing pattern during the synchronized activities generated by the intracortical circuit. By lowering extracellular Mg(2+) in vitro, we induced NMDA receptor-dependent spontaneous activities in the rat frontal cortex at 30 degrees C. After a series of spontaneous depolarization shifts, the long bursts occurred. The long bursts were composed of initial discharges and fast run-like potentials (FRLP) (4-10 Hz). Large inhibitory currents were induced at the initial discharge. After the strong inhibition decreased, the FRLP started. However, the periodical inhibition survived during the FRLP. At each phase of the synchronized activities, cortical neuron types exhibited distinct firing patterns. Pyramidal cells increased firing frequency periodically up to approximately 25-55 Hz during the FRLP cycles. Fast-spiking (FS) cells fired at the highest frequency in the initial discharge, up to 400 Hz, and could continue firing faster than 200 Hz for several seconds. In the FRLP, the firing frequency of FS cells rhythmically increased up to 150 Hz. In contrast, large cholecystokinin basket cells fired, very similarly to pyramidal cells, at each phase. Somatostatin and vasoactive intestinal polypeptide cells fired faster than pyramidal cells at the initial discharge, but showed the similar firings to pyramidal cells during the FRLP. The firing patterns of cortical neurons are not only determined by the strength and temporal pattern of synchronized inputs but also strongly dependent on the neuronal subtype with specific physiological, chemical, and morphological characteristics.

Spike transmission and synchrony detection in networks of GABAergic interneurons.

The temporal pattern and relative timing of action potentials among neocortical neurons may carry important information. However, how cortical circuits detect or generate coherent activity remains unclear. Using paired recordings in rat neocortical slices, we found that the firing of fast-spiking cells can reflect the spiking pattern of single-axon pyramidal inputs. Moreover, this property allowed groups of fast-spiking cells interconnected by electrical and gamma-aminobutyric acid (GABA)-releasing (GABAergic) synapses to detect the relative timing of their excitatory inputs. These results indicate that networks of fast-spiking cells may play a role in the detection and promotion of synchronous activity within the neocortex.

Fast spiking and regular spiking neural correlates of fear conditioning in the medial prefrontal cortex of the rat.

In order to investigate whether and how medial prefrontal cortex (mPFC) of the rat is involved in processing of information related to fear conditioning, we recorded from single units in the prelimbic and infralimbic cortex of fear-conditioned rats in response to an explicit conditional stimulus (CS; an auditory tone) or contextual cues (conditioning box). The majority of units changed their activities significantly in response to the CS in a delay or trace conditioning paradigm. Both transient and tonic activity changes, including delay cell activity, were observed as in other behavioral tasks. When exposed to the context without CS delivery, most units changed their activities as well. These results show that both tone and contextual information are processed in the rat mPFC in expectation of the delivery of an aversive stimulus (electric foot shock). Interestingly, fast spiking cells (putative inhibitory interneurons) and regular spiking cells (putative projection neurons) showed different patterns of responses. Fast spiking cells tended to show transient responses and increased their firing rates following CS presentation, whereas a complementary pattern was observed in the regular spiking cells. Our results enhance our understanding of the neural mechanisms underlying prediction of an aversive stimulus in the mPFC.

Kainate Receptors Regulate Unitary IPSCs Elicited in Pyramidal Cells by Fast-Spiking Interneurons in the Neocortex

Unitary IPSCs elicited by fast-spiking (FS) interneurons in layer V pyramidal cells of the neocortex were studied by means of dual whole-cell recordings in acute slices. FS to pyramidal cell unitary IPSCs were depressed by (RS)-S-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) (ATPA), a kainate (KA) receptor agonist, and by the endogenous agonist l-glutamate in the presence of AMPA, NMDA, mGluR, and GABA(B) receptor antagonists. This effect was accompanied by an increase in failure rate of synaptic transmission, in the coefficient of variation, and in the paired pulse ratio, indicating a presynaptic origin of the IPSC depression. Pairing the activation of the presynaptic neuron with a depolarization of the postsynaptic cell mimicked the decrease of unitary IPSCs, and this effect persisted when postsynaptic sodium action potentials were blocked with the local anesthetic QX314. The effects of ATPA, glutamate, and of the pairing protocol were almost totally blocked by CNQX. These data suggest that KA receptors located on presynaptic FS cell terminals decrease the release of GABA and can be activated by glutamate released from the somatodendritic compartment of the postsynaptic pyramidal cells.