Functional asymmetries in the rodent barrel cortex

Neurophysiological and 2-deoxyglucose (2DG) studies of the rodent whisker barrel cortex have demonstrated asymmetries in its functional organization. To examine the possibility that the activity gradients observed in metabolic studies can be attributed to subtle rostral-caudal and dorsal-ventral asymmetries in electrophysiologically measured surround or cross-whisker inhibition, we compared 2DG results with predictions generated from quantitative single-cell receptive field data. Despite differences in the two experimental approaches, there is remarkable agreement between the findings. (1) The distribution of 2DG activity declines across the barrel cortex of the behaving animal from anteromedial barrels to posterolateral barrels, and is qualitatively and quantitatively similar to the values predicted from neurophysiology. (2) The strength of surround inhibition in barrel neurons predicts the twofold increase in activation of the C3 barrel following acute clipping of adjacent whiskers. And (3) within a cortical column, the decrease in metabolic activity associated with adjacent whisker stimulation is greatest in layer IV and least in the infragranular layers; this corresponds to the laminar distribution of inhibitory interactions observed electrophysiologically.     

Polysynaptic subcircuits in the neocortex: spatial and temporal diversity

Inhibitory pathways in the neocortex display a variety of temporal and spatial patterns, maintaining a dynamic balance with excitatory synaptic activity. Recent studies have revealed prevalent polysynaptic subcircuits within the neocortical microcircuitry. These subcircuits involve excitatory and inhibitory connections that are activated by neurons both in supragranular and infragranular cortical layers and mediated by different mechanisms. Interestingly, in these subcircuits inhibition is induced by discharge of pyramidal cells, and excitation is caused by specific types of GABAergic interneurons. The different polysynaptic subcircuits are discussed with respect to their spatial and temporal properties and their possible functional role in cortical processing.     

Computer simulation of shared input among projection neurons in the dorsal cochlear nucleus

Computer simulations of a network model of an isofrequency patch of the dorsal cochlear nucleus (DCN) were run to explore possible mechanisms for the level-dependent features observed in the cross-correlograms of pairs of type IV units in the cat and nominal type IV units in the gerbil DCN. The computer model is based on the conceptual model (of a cat) that suggests two sources of shared input to DCN's projection neurons (type IV units): excitatory input from auditory nerves and inhibitory input from interneurons (type II units). Use of tonal stimuli is thought to cause competition between these sources resulting in the decorrelation of type IV unit activities at low levels. In the model, P-cells (projection neurons), representing type IV units, receive inhibitory input from I-cells (interneurons), representing type II units. Both sets of model neurons receive a simulated excitatory auditory nerve (AN) input from same-CF AN fibers, where the AN input is modeled as a dead-time modified Poisson process whose intensity is given by a computationally tractable discharge rate versus sound pressure level function. Subthreshold behavior of each model neuron is governed by a set of normalized state equations. The computer model has previously been shown to reproduce the major response properties of both type IV and type II units (e.g., rate-level curves and peri-stimulus time histograms) and the level-dependence of the functional type II-type IV inhibitory interaction. This model is adapted for the gerbil by simulating a reduced population of I-cells. Simulations were carried out for several auditory nerve input levels, and cross-correlograms were computed from the activities of pairs of P-cells for a complete (cat model) and reduced (gerbil model) population of I-cells. The resultant correlograms show central mounds (CMs), indicative of either shared excitatory or inhibitory input, for both spontaneous and tone-evoked driven activities. Similar to experimental results, CM amplitudes are a non-monotonic function of level and CM widths decrease as a function of level. These results are consistent with the hypothesis that shared excitatory input correlates the spontaneous activities of type IV units and shared inhibitory input correlates their driven activities. The results also suggest that the decorrelation of the activities of type IV units can result from a reduced effectiveness of the AN input as a function of increasing level. Thus, competition between the excitatory and inhibitory inputs is not required.     

Role of GABAA-Mediated Inhibition and Functional Assortment of Synapses onto Individual Layer 4 Neurons in Regulating Plasticity Expression in Visual Cortex

Layer 4 (L4) of primary visual cortex (V1) is the main recipient of thalamocortical fibers from the dorsal lateral geniculate nucleus (LGN_d). Thus, it is considered the main entry point of visual information into the neocortex and the first anatomical opportunity for intracortical visual processing before information leaves L4 and reaches supra- and infragranular cortical layers. The strength of monosynaptic connections from individual L4 excitatory cells onto adjacent L4 cells (unitary connections) is highly malleable, demonstrating that the initial stage of intracortical synaptic transmission of thalamocortical information can be altered by previous activity. However, the inhibitory network within L4 of V1 may act as an internal gate for induction of excitatory synaptic plasticity, thus providing either high fidelity throughput to supragranular layers or transmittal of a modified signal subject to recent activity-dependent plasticity. To evaluate this possibility, we compared the induction of synaptic plasticity using classical extracellular stimulation protocols that recruit a combination of excitatory and inhibitory synapses with stimulation of a single excitatory neuron onto a L4 cell. In order to induce plasticity, we paired pre- and postsynaptic activity (with the onset of postsynaptic spiking leading the presynaptic activation by 10ms) using extracellular stimulation (ECS) in acute slices of primary visual cortex and comparing the outcomes with our previously published results in which an identical protocol was used to induce synaptic plasticity between individual pre- and postsynaptic L4 excitatory neurons. Our results indicate that pairing of ECS with spiking in a L4 neuron fails to induce plasticity in L4-L4 connections if synaptic inhibition is intact. However, application of a similar pairing protocol under GABA_ARs inhibition by bath application of 2μM bicuculline does induce robust synaptic plasticity, long term potentiation (LTP) or long term depression (LTD), similar to our results with pairing of pre- and postsynaptic activation between individual excitatory L4 neurons in which inhibitory connections are not activated. These results are consistent with the well-established observation that inhibition limits the capacity for induction of plasticity at excitatory synapses and that pre- and postsynaptic activation at a fixed time interval can result in a variable range of plasticity outcomes. However, in the current study by virtue of having two sets of experimental data, we have provided a new insight into these processes. By randomly mixing the assorting of individual L4 neurons according to the frequency distribution of the experimentally determined plasticity outcome distribution based on the calculated convergence of multiple individual L4 neurons onto a single postsynaptic L4 neuron, we were able to compare then actual ECS plasticity outcomes to those predicted by randomly mixing individual pairs of neurons. Interestingly, the observed plasticity profiles with ECS cannot account for the random assortment of plasticity behaviors of synaptic connections between individual cell pairs. These results suggest that connections impinging onto a single postsynaptic cell may be grouped according to plasticity states.     

Confluence of barosensory and nonbarosensory inputs at neurons in the ventrolateral medulla in rabbits

In urethane-anesthetized rabbits, 209 spontaneously active neurons that responded to stimulation of aortic nerve A fibers were found within the ventrolateral medulla (VLM). The neurons, termed barosensory VLM neurons, were inhibited, except for three instances, by stimulation of A fibers. Forty-seven percent of barosensory VLM neurons tested (74 of 159) were activated antidromically by electrical stimulation of the dorsolateral funiculus at the C2 level. Activity of barosensory VLM neurons was enhanced by stimulation of carotid body chemoreceptors or the posterior hypothalamic area, whereas it was diminished by increases in arterial pressure elicited by injection of phenylephrine. Barosensory VLM neurons responded variously to stimulation, with two to three pulses at 40 or 100 Hz, of spinal afferents of cutaneous and muscle origins and the spinal trigeminal complex. Although stimulation of one group of somatosensory fibers could evoke different patterns of neuronal responses consisting of excitatory and inhibitory components, the following responses were most often encountered. Group II cutaneous afferents caused an inhibition. Recruitment of group III afferents brought about a brief excitatory component preceding it. Activation of group IV cutaneous fibers added a long latency excitatory component. Excitation of groups III and IV muscle afferents most often resulted in an inhibition, whereas stimulation of the spinal trigeminal complex elicited various combinations of excitatory and inhibitory components. These results are consistent with the view that neurons in the ventrolateral medulla receive barosensory and nonbarosensory inputs from various peripheral and central sources and participate in the control of sympathetic vasomotor activity and arterial pressure.     

Activation of a wide-spread network of inhibitory neurons in barrel cortex

Abstract The one-to-one correspondence of whiskers to barrels in layer IV of rodent somatosensory cortex can be demonstrated by a precise match between columns of heavy 2-deoxyglucose (2DG) label in layer IV barrels and other layers which correspond to stimulated whiskers. While there is specificity of peripheral-to-central mapping, the extent to which integration and/or modulation are generated by circuitry within or interactions between the barrel-defined whisker columns is not clear. Following stimulation of selected whiskers, large cells at the layer IV-V boundary throughout the barrel field are heavily labeled by 2-deoxyglucose (2DG) at high resolution. Many of these cells are outside the barrel columns of the stimulated whiskers. Further, the number of cells labeled is not directly related to the number of activated barrel columns. These neurons are not labeled in animals anesthetized before 2DG injection and are not as heavily labeled in barrel fields of somnolent animals. Most of the heavily labeled neurons immunolabel for glutamate decarboxylase (GAD) and are presumed to be inhibitory, while a smaller number of labeled neurons, presumed to be excitatory, immunolabel for glutamate (Glu). Similar populations of large, heavily 2DG-labeled neurons are found in other cortical areas. These relatively few neurons are exceptionally active and may modulate integrative functions of cerebral cortex.     

Axonal conduction properties of antidromically identified neurons in rat barrel cortex

Physiological studies of the rodent somatosensory cortex have consistently described considerable heterogeneity in receptive field properties of neurons outside of layer IV, particularly those in layers V and VI. One such approach for distinguishing among different local circuits in these layers may be to identify the projection target of neurons whose axon collaterals contribute to the local network. In vivo, this can be accomplished using antidromic stimulation methods. Using this approach, the axonal conduction properties of cortical efferent neurons are described. Four projection sites were activated using electrical stimulation: (1) vibrissal motor cortex, (2) ventrobasal thalamus (VB), (3) posteromedial thalamic nucleus (POm), and (4) cerebral peduncle. Extracellular recordings were obtained from a total of 169 units in 21 animals. Results demonstrate a close correspondence between the laminar location of the antidromically identified neurons and their anatomically known layer of origin. Axonal properties were most distinct for corticofugal axons projecting through the crus cerebri. Corticothalamic axons projecting to either VB or POm were more similar to each other in terms of laminar location and conduction properties, but could be distinguished using focal electrical stimulation. It is concluded that, once stimulation parameters are adjusted for the small volume of the rat brain, the use of antidromic techniques may be an effective strategy to differentiate among projection neurons comprising different local circuits in supra- and infragranular circuits.     

Axonal Dynamics of Excitatory and Inhibitory Neurons in Somatosensory Cortex

Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.     

Activity-dependent matching of excitatory and inhibitory inputs during refinement of visual receptive fields

The receptive field (RF) of single visual neurons undergoes progressive refinement during development. It remains largely unknown how the excitatory and inhibitory inputs on single developing neurons are refined in a coordinated manner to allow the formation of functionally correct circuits. Using whole-cell voltage-clamp recording from Xenopus tectal neurons, we found that RFs determined by excitatory and inhibitory inputs in more mature tectal neurons are spatially matched, with each spot stimulus evoking balanced synaptic excitation and inhibition. This emerges during development through a gradual reduction in the RF size and a transition from disparate to matched topography of excitatory and inhibitory inputs to the tectal neurons. Altering normal spiking activity of tectal neurons by either blocking or elevating GABA(A) receptor activity significantly impeded the developmental reduction and topographic matching of RFs. Thus, appropriate inhibitory activity is essential for the coordinated refinement of excitatory and inhibitory connections.     

Axonal conduction properties of antidromically identified neurons in rat barrel cortex

Physiological studies of the rodent somatosensory cortex have consistently described considerable heterogeneity in receptive field properties of neurons outside of layer IV, particularly those in layers V and VI. One such approach for distinguishing among different local circuits in these layers may be to identify the projection target of neurons whose axon collaterals contribute to the local network. In vivo, this can be accomplished using antidromic stimulation methods. Using this approach, the axonal conduction properties of cortical efferent neurons are described. Four projection sites were activated using electrical stimulation: (1) vibrissal motor cortex, (2) ventrobasal thalamus (VB), (3) posteromedial thalamic nucleus (POm), and (4) cerebral peduncle. Extracellular recordings were obtained from a total of 169 units in 21 animals. Results demonstrate a close correspondence between the laminar location of the antidromically identified neurons and their anatomically known layer of origin. Axonal properties were most distinct for corticofugal axons projecting through the crus cerebri. Corticothalamic axons projecting to either VB or POm were more similar to each other in terms of laminar location and conduction properties, but could be distinguished using focal electrical stimulation. It is concluded that, once stimulation parameters are adjusted for the small volume of the rat brain, the use of antidromic techniques may be an effective strategy to differentiate among projection neurons comprising different local circuits in supra- and infragranular circuits.     

Neurogliaform cells: neurochemistry, spatial arrangement, and their role in the neocortical inhibitory system

The neurogliaform cells (NGFC) localized in area 4 of the human motor cortex were found to express choline acetyl transferase (ChAT), GABA, and calbindin. ChAT-positive neurons were located in cortical layer II. Their dendrites lay in a close proximity to those of pyramid cells, neighbouring neurogliaform cells, and bodies and dendrites of other cortical neurons. The NGFCs revealed by Golgi staining fell into two groups. Cells of the first group had locally (within cortical layer II) spreading axons, while those of the second group had axons extending into the adjacent layers. Neurochemical heterogeneity of NGFCs is discussed in the context of information processing in cortical modules and interaction of excitatory and inhibitory interneurons.     

Single cell responses from the optic tectum of the zebra finch (Taeniopygia guttata castanotis Gould)

Responses of neurons of the optic tectum, the prominent, highly laminated mesencephalic station of the tectofugal visual pathway in birds, to computer-generated and other visual stimuli were examined in zebra finches. Our study shows that the contralateral retina projects to the tectum in topographic order. The representation of the visual field is tilted against the horizon by 22°. The representation of the contralateral hemifield extends to the ipsilateral side by 15°. Most neurons have receptive fields with excitatory centres of different shapes and inhibitory surround. A new type of neuronal receptive field is described which has an excitatory centre and a surround which is movement sensitive and preferably excited by very small spots. The first type of neurons is mostly located in upper tectal layers, the latter only in deeper layers. Excitatory centre sizes increase with depth, and there is a tendency of smaller receptive fields in the foveal region. The representation of the frontal visual field does not show specializations which could be expected if it were used for fixation of grain during pecking. Our results are in accordance with previous behavioural experiments. Accepted: 30 April 1999     

Thalamocortical control of feed-forward inhibition in awake somatosensory 'barrel' cortex

Intracortical inhibition plays a role in shaping sensory cortical receptive fields and is mediated by both feed-forward and feedback mechanisms. Feed-forward inhibition is the faster of the two processes, being generated by inhibitory interneurons driven by monosynaptic thalamocortical (TC) input. In principle, feed-forward inhibition can prevent targeted cortical neurons from ever reaching threshold when TC input is weak. To do so, however, inhibitory interneurons must respond to TC input at low thresholds and generate spikes very quickly. A powerful feed-forward inhibition would sharpen the tuning characteristics of targeted cortical neurons, and interneurons with sensitive and broadly tuned receptive fields could mediate this process. Suspected inhibitory interneurons (SINs) with precisely these properties are found in layer 4 of the somatosensory (S1) 'barrel' cortex of rodents and rabbits. These interneurons lack the directional selectivity seen in most cortical spiny neurons and in ventrobasal TC afferents, but are much more sensitive than cortical spiny neurons to low-amplitude whisker displacements. This paper is concerned with the activation of S1 SINs by TC impulses, and with the consequences of this activation. Multiple TC neurons and multiple S1 SINs were simultaneously studied in awake rabbits, and cross-correlation methods were used to examine functional connectivity. The results demonstrate a potent, temporally precise, dynamic and highly convergent/divergent functional input from ventrobasal TC neurons to SINs of the topographically aligned S1 barrel. Whereas the extensive pooling of convergent TC inputs onto SINs generates sensitive and broadly tuned inhibitory receptive fields, the potent TC divergence onto many SINs generates sharply synchronous activity among these elements. This TC feed-forward inhibitory network is well suited to provide a fast, potent, sensitive and broadly tuned inhibition of targeted spiny neurons that will suppress spike generation following all but the most optimal feed-forward excitatory inputs.     

Effect of chronic morphine exposure on response properties of rat barrel cortex neurons.

Chronic exposure to morphine can impair performance in tasks which need sensory processing. Using single unit recordings we investigate the effect of chronic morphine exposure on the firing properties of neurons in layers IV and V of the whisker-related area of rat primary somatosensory cortex. In urethane-anesthetized animals, neuronal activity was recorded in response to principal and adjacent whisker deflections either stimulated independently or in a conditioning test paradigm. A condition test ratio (CTR) was calculated for assessing the inhibitory receptive field. In layer IV, chronic morphine treatment did not change the spontaneous discharge activity. On responses to principal and adjacent whisker deflections did not show any significant changes following chronic morphine exposure. The magnitude Off responses to adjacent whisker deflection decreased while its response latency increased. In addition, there was a significant increase in the latency of Off responses to principal whisker deflection. CTR did not change significantly following morphine exposure. Layer V neurons, on the other hand, did not show any significant changes in their spontaneous activity or their evoked responses following morphine exposure. Our results suggest that chronic morphine exposure has a subtle modulatory effect on response properties of neurons in barrel cortex.     

Neurons with complex receptive fields in the stratum griseum centrale of the zebra finch (Taeniopygia guttata castanotis Gould) optic tectum

The electrophysiological and morphological features of visually driven neurons of the stratum griseum centrale of the zebra finch optic tectum were studied by extracellular recording and staining techniques. Stratum griseum centrale neuron responses are sustained in most cases. Receptive fields are big, up to 150 degrees of the visual field. The excitatory center (hot spot) varies in size from 1 degrees to 15 degrees. It can be mapped by small static stimuli, adapts slower than the surround, and has a shape comparable to the excitatory fields of upper-layer neurons. In contrast, the big surround shows responses only to small moving objects which elicit a typical pattern of alternating bursts and silent periods. Alternatively, the same stimuli elicit long-lasting bursts followed by strong adaption. Anatomically, stratum griseum centrale neurons are characterized by far reaching dendrites which terminate with "bottlebrush"-like endings in the upper retinorecipient layers. In addition, they are connected with retinorecipient structures by an interneuron located between layers 10 and 11. The role of the structure of inputs for the organization of the receptive fields is discussed.     

Effect of Contrast on Visual Spatial Summation in Different Cell Categories in Cat Primary Visual Cortex

Multiple cell classes have been found in the primary visual cortex, but the relationship between cell types and spatial summation has seldom been studied. Parvalbumin-expressing inhibitory interneurons can be distinguished from pyramidal neurons based on their briefer action potential durations. In this study, we classified V1 cells into fast-spiking units (FSUs) and regular-spiking units (RSUs) and then examined spatial summation at high and low contrast. Our results revealed that the excitatory classical receptive field and the suppressive non-classical receptive field expanded at low contrast for both FSUs and RSUs, but the expansion was more marked for the RSUs than for the FSUs. For most V1 neurons, surround suppression varied as the contrast changed from high to low. However, FSUs exhibited no significant difference in the strength of suppression between high and low contrast, although the overall suppression decreased significantly at low contrast for the RSUs. Our results suggest that the modulation of spatial summation by stimulus contrast differs across populations of neurons in the cat primary visual cortex.     

Timing and specificity of feed-forward inhibition within the LGN

Local interneurons provide feed-forward inhibition from retinal ganglion cells (RGCs) to thalamocortical (TC) neurons, but questions remain regarding the timing, magnitude, and functions of this inhibition. Here, we identify two types of inhibition that are suited to play distinctive roles. We recorded excitatory and inhibitory postsynaptic currents (EPSCs/IPSCs) in TC neurons in mouse brain slices and activated individual RGC inputs. In 34% of TC neurons, we identified EPSCs and IPSCs with identical thresholds that were tightly correlated, indicating activation by the same RGC. Such "locked" IPSCs occurred 1 ms after EPSC onset. The remaining neurons had only "nonlocked" inhibition, in which EPSCs and IPSCs had different thresholds, indicating activation by different RGCs. Nonlocked inhibition may refine receptive fields within the LGN by providing surround inhibition. In contrast, dynamic-clamp recordings suggest that locked inhibition improves the precision of synaptically evoked responses in individual TC neurons by eliminating secondary spikes.     

Somatosensory integration controlled by dynamic thalamocortical feed-forward inhibition

The temporal features of tactile stimuli are faithfully represented by the activity of neurons in the somatosensory cortex. However, the cellular mechanisms that enable cortical neurons to report accurate temporal information are not known. Here, we show that in the rodent barrel cortex, the temporal window for integration of thalamic inputs is under the control of thalamocortical feed-forward inhibition and can vary from 1 to 10 ms. A single thalamic fiber can trigger feed-forward inhibition and contacts both excitatory and inhibitory cortical neurons. The dynamics of feed-forward inhibition exceed those of each individual synapse in the circuit and are captured by a simple disynaptic model of the thalamocortical projection. The variations in the integration window produce changes in the temporal precision of cortical responses to whisker stimulation. Hence, feed-forward inhibitory circuits, classically known to sharpen spatial contrast of tactile inputs, also increase the temporal resolution in the somatosensory cortex.     

TrkB受体依赖的PV神经元调控小鼠视觉方位辨别能力的机制

神经营养因子-酪氨酸受体激酶B （tyrosine receptor kinase B,TrkB）信号通路在调控初级视皮层（primary visual cortex,V1）兴奋与抑制平衡上发挥着重要的作用,以往的研究揭示了其通过增加兴奋性传递效率来调控皮层兴奋性水平的机制,却并未阐明TrkB受体如何通过抑制系统来调控兴奋与抑制平衡,进而影响视觉皮层功能。为了探讨TrkB信号通路如何特异性地调控最主要的抑制性神经元——PV神经元进而对小鼠视觉皮层功能产生影响,本研究通过病毒特异性地降低V1区的PV神经元上TrkB受体的表达水平,并通过在体多通道电生理手段记录初级视皮层抑制性与兴奋性神经元功能变化,通过行为学实验测试小鼠的方位辨别能力改变。结果表明,初级视觉皮层中的PV抑制性神经元上的TrkB受体表达减少会显著增加兴奋性神经元的反应强度,减弱抑制性神经元与兴奋性神经元的方位辨别能力,增加二者的信噪比,但是小鼠个体水平的方位辨别能力出现下降。这些结果说明,TrkB信号通路并非单纯通过增加靶向PV神经元的兴奋性传递来调控PV神经元的功能,其对神经元信噪比的影响也并非由于抑制系统的增强所致。