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The mammalian telencephalon is responsible for many functions, which range from processing sensory information to learning, decision-making, and modulating emotional responses. The telencephalon's capacity to perform such a variety of functions likely relies on its neuronal diversity. Interneurons, with their enormous multiplicity of subtypes are a primary contributor to this repertoire. Each inhibitory interneuron subclass likely possesses both a unique connectivity and an input/output function that defines its diverse role in the telencephalon.

Even a simple sensory stimulus can elicit distinct innate behaviors and sequences. During sensorimotor decisions, competitive interactions among neurons that promote distinct behaviors must ensure the selection and maintenance of one behavior, while suppressing others. The circuit implementation of these competitive interactions is still an open question. By combining comprehensive electron microscopy reconstruction of inhibitory interneuron networks, modeling, electrophysiology, and behavioral studies, we determined the circuit mechanisms that contribute to the Drosophila larval sensorimotor decision to startle, explore, or perform a sequence of the two in response to a mechanosensory stimulus. Together, these studies reveal that, early in sensory processing, (1) reciprocally connected feedforward inhibitory interneurons implement behavioral choice, (2) local feedback disinhibition provides positive feedback that consolidates and maintains the chosen behavior, and (3) lateral disinhibition promotes sequence transitions. The combination of these interconnected circuit motifs can implement both behavior selection and the serial organization of behaviors into a sequence.

Amacrine and horizontal interneurons integrate visual information as it is relayed through the retina from the photoreceptors to the ganglion cells. The early steps that generate these interneuron networks remain unclear. Here we show that a distinct retinoid-related orphan nuclear receptor β1 (RORβ1) isoform encoded by the retinoid-related orphan nuclear receptor β gene (Rorb) is critical for both amacrine and horizontal cell differentiation in mice. A fluorescent protein cassette targeted into Rorb revealed RORβ1 as a novel marker of immature amacrine and horizontal cells and of undifferentiated, dividing progenitor cells. RORβ1-deficient mice lose expression of pancreas-specific transcription factor 1a (Ptf1a) but retain forkhead box n4 factor (Foxn4), two early-acting factors necessary for amacrine and horizontal cell generation. RORβ1 and Foxn4 synergistically induce Ptf1a expression, suggesting a central role for RORβ1 in a transcriptional hierarchy that directs this interneuron differentiation pathway. Moreover, ectopic RORβ1 expression in neonatal retina promotes amacrine cell differentiation.

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Between 25–40% of neurons in laminae I–III are GABAergic, and some of these express neuropeptide Y (NPY). We previously reported that NPY-immunoreactive axons form numerous synapses on lamina III projection neurons that possess the neurokinin 1 receptor (NK1r). The aims of this study were to determine the proportion of neurons and GABAergic boutons in this region that contain NPY, and to look for evidence that they selectively innervate different neuronal populations. We found that 4–6% of neurons in laminae I–III were NPY-immunoreactive and based on the proportions of neurons that are GABAergic, we estimate that NPY is expressed by 18% of inhibitory interneurons in laminae I–II and 9% of those in lamina III. GABAergic boutons were identified by the presence of the vesicular GABA transporter (VGAT) and NPY was found in 13–15% of VGAT-immunoreactive boutons in laminae I–II, and 5% of those in lamina III. For both the lamina III NK1r-immunoreactive projection neurons and protein kinase Cγ (PKCγ)-immunoreactive interneurons in lamina II, we found that around one-third of the VGAT boutons that contacted them were NPY-immunoreactive. However, based on differences in the sizes of these boutons and the strength of their NPY-immunoreactivity, we conclude that these originate from different populations of interneurons. Only 6% of VGAT boutons presynaptic to large lamina I projection neurons that lacked NK1rs contained NPY. These results show that NPY-containing neurons make up a considerable proportion of the inhibitory interneurons in laminae I–III, and that their axons preferentially target certain classes of dorsal horn neuron. J. Comp. Neurol. 519:1007–1023, 2011. © 2010 Wiley-Liss, Inc.

International audience; In this article, we will review molecular, anatomical, physiological and pharmacological data in an attempt to better understand how excitatory and inhibitory neurons recruited by distinct afferent inputs to the cerebral cortex contribute to the coupled hemodynamic response, and how astrocytes can act as intermediaries to these neuronal populations. We aim at providing the pros and cons to the following statements that, depending on the nature of the afferent input to the neocortex, (i) different neuronal or astroglial messengers, likely acting in sequence, mediate the hemodynamic changes, (ii) some recruited neurons release messengers that directly alter blood vessel tone, (iii) others act by modulating neuronal and astroglial activity, and (iv) astrocytes act as intermediaries for both excitatory and inhibitory neurotransmitters. We will stress that a given afferent signal activates a precise neuronal circuitry that determines the mediators of the hemodynamic response as well as the level of interaction with surrounding astrocytes.

We consider a layer of excitatory neurons with small asymmetric excitatory connections and strong coupling to a single inhibitory interneuron. If the inhibition is fast, the network behaves as a winner-take-all network in which one cell fires at the expense of all others. As the inhibition slows down, oscillatory behavior begins. This is followed by a symmetric rotating solution in which neurons share the activity in a round-robin fashion. Finally, if the inhibition is sufficiently slower than excitation the neurons completely synchronize to a global periodic solution. Conditions guaranteeing stable synchrony are given.

Simulations were performed of physiological interactions among excitatory and inhibitory neurons in anatomically realistic local-circuit architectures modeled after hippocampal field CA1. The simulated circuitry consists of several excitatory neurons jointly innervating and receiving feedback from a common inhibitory interneuron. Excitatory cells in the simulation receive input during a cycle of naturally-occurring rhythmic activity (the hippocampal theta rhythm), and the neuron receiving the most input activation is the first to reach its spiking threshold. Spiking excites the inhibitory cell, which in turn prevents other cells from responding. The result is the natural generation of a simple competitive or ''winner-take-all'' (WTA) mechanism, allowing only the most strongly-activated cell in a group or ''patch'' to respond with spiking activity. Formal mathematical characterization of the mechanism reveals specific physiological characteristics of the input to the network, which enable it to closely approximate an ideal winner-take-all mechanism. Unlike other, more abstract WTA mechanisms that have been proposed, the parameters of this biologically-derived WTA mechanism can be directly related to specific physiological and anatomical features of particular cortical circuits.

We will consider the dynamics of attractor neural networks with sign-constrained weights. In the presense of sign-constraints on weights three types of attractor can affect the dynamics: retrieval attractors, spurious attractors and uniform attractors. The uniform attracting states can dominate the dynamics if there is a substantial weight-sign bias. We will show that it is possible to define dynamic thresholds for a variety of learning rules which can eliminate uniform attracting states for any value of the weight-sign bias.

The Fast Spiking (FS) interneurons are coupled by both electrical and inhibitory synapses and experimental findings suggest that they operate as a clockwork affecting the processing of neural information. At present, it is not known which is the functional role of electrical synapses in a network of inhibitory interneurons. In our contribution, by using a single compartment biophysical model of an FS cell, we determine the parameter values leading to the emergence of synchronous regimes in a network of FS interneurons coupled by chemical and electrical synapses. We also compare our results with those recently obtained for a pair of coupled Integrate & Fire neural models [1].

In recurrent neural networks, excessive activity oscillations can be very disruptive to successful learning performance. Inhibitory feedback can be used to offset a dominating positive feedback; however, synaptic modification at excitatory synapses would seem to require synaptic modification at inhibitory synapses if activity is to be controlled during training. Here, we present a novel synaptic modification rule that governs the synaptic strength of afferents (inputs) to activity controlling inhibitory interneurons. A hippocampal CA3 model incorporating this rule can avoid certain performance destroying activity oscillations. In the minimal model used here, this new rule for synaptic modification implements an error-correcting-like procedure at each excitatory input to a global feedback inhibitory interneuron. Simulations that include this novel modification rule demonstrate robust sequence learning as well as the elimination of major activity fluctuations that are outside the biologically plausible range. Importantly, simulations using this rule are able to adapt quickly and selectively to large, discontinuous jumps in the training sequences.

The role of activity-dependent plasticity in modulating inhibitory synapses was investigated in embryonic rat spinal cord slice cultures, by chronic exposure to non-NMDA receptor blockers. GABAergic synaptic efficacy in control and chronic-treated cultures was investigated by patch-recordings from visually identified spinal interneurons. In both culture groups proximal stimulation induced the appearance of postsynaptic currents (PSCs), which were fully antagonized by 20 microM bicuculline application and reverse polarity at potential values close to those reported for spontaneous GABAergic PSCs. In chronically treated cells GABAergic evoked PSCs displayed a larger failure rate and a smaller coefficient of variation of mean PSC amplitude, when compared to controls. As opposed to controls, chronic GABAergic evoked PSCs did not facilitate upon paired-pulse stimulation. Facilitation at chronic synapses was observed when extracellular calcium levels were decreased below physiological values (< 2 mM). Kainate was used to disclose any functional differences between control and treated slices. In accordance with the presynaptic action of kainate, the application of this drug along with GYKI, an AMPA receptor selective antagonist, changed, with analogous potency, short-term plasticity of GABAergic synapses from control and treated cultures. Nevertheless, in chronic cultures, the downstream effects of such activation unmasked short-term depression. Ultrastructural analysis of synapses in chronically treated cultures showed a reduction both in symmetric synapses and in the number of vesicles at symmetric terminals. Thus, based on electrophysiological and ultrastructural data, it could be suggested that during the development of spinal circuits, GABAergic synapses are modulated by glutamatergic transmission, and thus implying that excitatory transmission regulates the strength of GABAergic synapses.

Experimental data recorded in cat in vivo offer a new picture of the cuneate nucleus. Classically defined as a simple relay station, the cuneate nucleus is currently seen as a fundamental stage in somatosensory information processing. Intracellular and extracellular recordings have revealed a complex circuitry established by cuneothalamic cells, interneurons and afferent fibers from the sensorimotor cortex. As a result of electrophysiological work, some circuits have been hypothesized in order to explain the data. In this paper we present a computational model designed and developed in order to test the validity of the proposed circuit in [15]. The results of the computer simulations support the predictions.

Publisher Summary This chapter presents some experiments and simulations of the segmental burst-generating network used in lamprey locomotion. The motor pattern in each segment constitutes a strictly alternating burst activity between the left and the right side. Each motoneuron is depolarized during ipsilateral burst activity and inhibited during contralateral activity. The inhibition is produced by contralateral interneurons (CCIN), which produce inhibitory postsynaptic potentials utilizing glycine as neuronal transmitter. The excitation is produced by ipsilateral interneurons (EIN), which activate glutamate receptors and are active during the ipsilateral burst activity. Finally, an ipsilateral inhibitory interneuron is active in synchrony with EIN, and it inhibits the ipsilateral inhibitory CCIN.

This Golgi study identifies a class of small neurons in trigeminal nucleus oralis (Vo) that satisfies all the morphological criteria for a Golgi Type II neuron. The cylindrical-shaped dendritic arbor extends up to 500 μm in the rostrocaudal axis and is confined to Vo. The unmyelinated axon generates a highly branched collateral axonal plexus within or near the dendritic tree and it does not project out of Vo. This Golgi Type II neuron is considered to be an inhibitory interneuron and probably participates in a variety of inhibitory phenomena known to occur in Vo.

Publisher Summary This chapter discusses interpretations of the functional role of the gamma system in the light of experimental work. Among major themes might be mentioned (1) spinal alphagamma linkage in reciprocal innervation, (2) in relation to slow and fast muscles, the alternatives of alpha respectively gamma precedence in their coactivation, (3) the compensatory response to unexpected loading, (4) gain control in relation to vibratory reflexes, (5) mono- and polysynaptic spindle control of motor activity, (6) the role of the gamma system in maximizing motor effects, and others. The existence of a spinal stepping generator in combination with the detailed knowledge of the supraspinal control of the Ia inhibitory interneuron given by the Gothenburg workers means that the mechanism employing reciprocal innervation must be activated in a well-organized manner when started supraspinally, for instance, by mesencephalic stimulation as introduced by Shik et al. This perfect spinal timing instrument can of course be wrongly approached by a supraspinal governor and this is likely to have happened in the experiments of Brooks in which local cooling of globus pallidus led to a breakdown of alternating movements.

Decay of the late RP (receptor potential) becomes very slow when the stimulus intensity for saturating amplitude of the late RP is exceeded. In macaque monkey this was shown earlier for the rod late RP, and is now shown at higher stimulus intensities for the cone late RP. These slowly decaying responses to “overdriving” stimuli are referred to, respectively, asrod andcone aftereffects. Since these aftereffects greatly prolong the response to a given stimulus, they must degrade the ability of the visual system to resolve stimuli in the time domain. For the rod late RP our preceding paper shows that this problem is handled by suppression of the rod late RP at photopic intensities, apparently by a cone-initiated pathway acting through the horizontal cell as inhibitory interneuron. In this paper we show that the cone aftereffect, which occurs only at high photopic intensities, is quickly dissipated by light adaptation at those intensities. In other words, light adaptation is highly effective in protecting against the cone aftereffect. The cones are thus capable of resolving stimuli in the time domain at considerably higher stimulus intensities than would otherwise be possible. This provides a significant upward extension of the intensity range of useful vision.