Academic literature on the topic 'Inhibitory Neurons'

Our goal is to examine the relationship between neuron- and network-level processing in the context of a well-studied cortical function, the processing of thalamic input by whisker-barrel circuits in rodent neocortex. Here we focus on neuron-level processing and investigate the responses of excitatory and inhibitory barrel neurons to simulated thalamic inputs applied using the dynamic clamp method in brain slices. Simulated inputs are modeled after real thalamic inputs recorded in vivo in response to brief whisker deflections. Our results suggest that inhibitory neurons require more input to reach firing threshold, but then fire earlier, with less variability, and respond to a broader range of inputs than do excitatory neurons. Differences in the responses of barrel neuron subtypes depend on their intrinsic membrane properties. Neurons with a low input resistance require more input to reach threshold but then fire earlier than neurons with a higher input resistance, regardless of the neuron's classification. Our results also suggest that the response properties of excitatory versus inhibitory barrel neurons are consistent with the response sensitivities of the ensemble barrel network. The short response latency of inhibitory neurons may serve to suppress ensemble barrel responses to asynchronous thalamic input. Correspondingly, whereas neurons acting as part of the barrel circuit in vivo are highly selective for temporally correlated thalamic input, excitatory barrel neurons acting alone in vitro are less so. These data suggest that network-level processing of thalamic input in barrel cortex depends on neuron-level processing of the same input by excitatory and inhibitory barrel neurons.

In computational neural network models, neurons are usually allowed to excite some and inhibit other neurons, depending on the weight of their synaptic connections. The traditional way to transform such networks into networks that obey Dale's law (i.e., a neuron can either excite or inhibit) is to accompany each excitatory neuron with an inhibitory one through which inhibitory signals are mediated. However, this requires an equal number of excitatory and inhibitory neurons, whereas a realistic number of inhibitory neurons is much smaller. In this letter, we propose a model of nonlinear interaction of inhibitory synapses on dendritic compartments of excitatory neurons that allows the excitatory neurons to mediate inhibitory signals through a subset of the inhibitory population. With this construction, the number of required inhibitory neurons can be reduced tremendously.

A previously developed method for efficiently simulating complex networks of integrate-and-fire neurons was specialized to the case in which the neurons have fast unitary postsynaptic conductances. However, inhibitory synaptic conductances are often slower than excitatory ones for cortical neurons, and this difference can have a profound effect on network dynamics that cannot be captured with neurons that have only fast synapses. We thus extend the model to include slow inhibitory synapses. In this model, neurons are grouped into large populations of similar neurons. For each population, we calculate the evolution of a probability density function (PDF), which describes the distribution of neurons over state-space. The population firing rate is given by the flux of probability across the threshold voltage for firing an action potential. In the case of fast synaptic conductances, the PDF was one-dimensional, as the state of a neuron was completely determined by its transmembrane voltage. An exact extension to slow inhibitory synapses increases the dimension of the PDF to two or three, as the state of a neuron now includes the state of its inhibitory synaptic conductance. However, by assuming that the expected value of a neuron's inhibitory conductance is independent of its voltage, we derive a reduction to a one-dimensional PDF and avoid increasing the computational complexity of the problem. We demonstrate that although this assumption is not strictly valid, the results of the reduced model are surprisingly accurate.

Abstract The functional properties of neurons in the primary visual cortex (V1) are thought to be closely related to the structural properties of this network, but the specific relationships remain unclear. Previous theoretical studies have suggested that sparse coding, an energy-efficient coding method, might underlie the orientation selectivity of V1 neurons. We thus aimed to delineate how the neurons are wired to produce this feature. We constructed a model and endowed it with a simple Hebbian learning rule to encode images of natural scenes. The excitatory neurons fired sparsely in response to images and developed strong orientation selectivity. After learning, the connectivity between excitatory neuron pairs, inhibitory neuron pairs, and excitatory-inhibitory neuron pairs depended on firing pattern and receptive field similarity between the neurons. The receptive fields (RFs) of excitatory neurons and inhibitory neurons were well predicted by the RFs of presynaptic excitatory neurons and inhibitory neurons, respectively. The excitatory neurons formed a small-world network, in which certain local connection patterns were significantly overrepresented. Bidirectionally manipulating the firing rates of inhibitory neurons caused linear transformations of the firing rates of excitatory neurons, and vice versa. These wiring properties and modulatory effects were congruent with a wide variety of data measured in V1, suggesting that the sparse coding principle might underlie both the functional and wiring properties of V1 neurons.

Spinal gastrin-releasing peptide receptor-expressing (GRPR+) neurons play an essential role in itch signal processing. However, the circuit mechanisms underlying the modulation of spinal GRPR+neurons by direct local and long-range inhibitory inputs remain elusive. Using viral tracing and electrophysiological approaches, we dissected the neural circuits underlying the inhibitory control of spinal GRPR+neurons. We found that spinal galanin+GABAergic neurons form inhibitory synapses with GRPR+neurons in the spinal cord and play an important role in gating the GRPR+neuron-dependent itch signaling pathway. Spinal GRPR+neurons also receive inhibitory inputs from local neurons expressing neuronal nitric oxide synthase (nNOS). Moreover, spinal GRPR+neurons are gated by strong inhibitory inputs from the rostral ventromedial medulla. Thus, both local and long-range inhibitory inputs could play important roles in gating itch processing in the spinal cord by directly modulating the activity of spinal GRPR+neurons.

Neurons in area TE of the monkey inferior temporal cortex respond selectively to images of particular objects or their characteristic visual features. The mechanism of generation of the stimulus selectivity, however, is largely unknown. This study addresses the role of inhibitory TE neurons in this process by examining their visual response properties and interactions with adjacent target neurons. We applied cross-correlation analysis to spike trains simultaneously recorded from pairs of adjacent neurons in anesthetized macaques. Neurons whose activity preceded a decrease in activity from their partner were presumed to be inhibitory neurons. Excitatory neurons were also identified as the source neuron of excitatory linkage as evidenced by a sharp peak displaced from the 0-ms bin in cross-correlograms. Most inhibitory neurons responded to a variety of visual stimuli in our stimulus set, which consisted of several dozen geometrical figures and photographs of objects, with a clear stimulus preference. On average, 10% of the stimuli increased firing rates of the inhibitory neurons. Both excitatory and inhibitory neurons exhibited a similar degree of stimulus selectivity. Although inhibitory neurons occasionally shared the most preferred stimuli with their target neurons, overall stimulus preferences were less similar between adjacent neurons with inhibitory linkages than adjacent neurons with common inputs and/or excitatory linkages. These results suggest that inhibitory neurons in area TE are activated selectively and exert stimulus-specific inhibition on adjacent neurons, contributing to shaping of stimulus selectivity of TE neurons.

Spontaneous activities of vibrissa-responding neurons in the rat ventrobasal complex (VB) and somatosensory part of the thalamic reticular nucleus (S-TR) were simultaneously recorded and subjected to cross-correlation analysis to investigate the functional organization of recurrent inhibitory action of the S-TR on VB neurons. Excitatory and/or inhibitory interactions were found between approximately 75% (25/34) of the pairs of S-TR and VB neurons with receptive fields (RFs) on the same vibrissa. In contrast, there was no significant interaction between 54 pairs of neurons having RFs on different vibrissae. Among the pairs of neurons with RFs on the same vibrissa, there were four types of correlations, which indicate the following connections: monosynaptic excitation from a VB to an S-TR neuron (7 pairs), monosynaptic inhibition from an S-TR to a VB neuron (10 pairs), reciprocal connection combining the above two types (7 pairs), and common excitation in addition to inhibition from an S-TR to a VB neuron (1 pair). Examples of divergence and convergence of connections between S-TR and VB neurons were demonstrated by testing one S-TR (VB) neuron with more than one VB (S-TR) neuron. Vibrissa-suppressed VB cells, which had exclusively inhibitory RFs, were included in eight pairs of the above samples. These VB cells were more likely to receive inhibitory inputs from S-TR neurons than other VB neurons. Cells with RFs on multiple vibrissae were included in the other 10 pairs. These multiple-vibrissa cells had no interaction with single-vibrissa cells but did with multiple-vibrissa cells. From the incidence of four types of correlation between S-TR and VB neurons with RFs on the same vibrissa, the following connection pattern is suggested: One S-TR neuron receives excitatory inputs from approximately 40% of the VB neurons with RFs on the same vibrissa and sends inhibitory outputs to approximately 55%. Since these two groups of VB neurons were overlapping, the S-TR neuron has reciprocal connections with approximately 20% of the VB neurons with RFs on the same vibrissa. The same estimate was applied to connectivity of one VB neuron. These results indicate that both inputs and outputs of S-TR neurons are precisely and topographically organized, although there is convergence to and divergence from a substantial number of VB neurons with RFs on the same vibrissa. It is proposed that the recurrent inhibitory circuit through the S-TR plays a role in improving discrimination of sensory information transmitted through the VB.

Effects of somatostatin (SRIF) on neurons in the medial amygdaloid nucleus were investigated in rat brain slice preparations, using extracellular recordings. Following bath application of SRIF at 10−7–10−6 M, 63 of 81 (78%) medial amygdala neurons showed an inhibitory response. The inhibitory effect of SRIF was dose dependent, and the threshold concentration was approximately 10−9 M. The inhibitory response to SRIF persisted during synaptic blockade in two-thirds of neurons tested. The inhibitory effect of SRIF was reduced by picrotoxin, a GABAA receptor antagonist, in one-third of neurons. These results suggest that SRIF exerts an inhibitory effect on medial amygdala neurons through either a direct action on SRIF receptors or a GABAergic synaptic involvement.Key words: somatostatin, amygdala, brain slice, neuron activity, picrotoxin.

Cortical inhibitory neurons play crucial roles in regulating excitatory synaptic networks and cognitive function and aberrant development of these cells have been linked to neurodevelopmental disorders. The secreted neurotrophic factor Neuregulin-1 (NRG1) and its receptor ErbB4 are established regulators of inhibitory neuron connectivity, but the developmental signalling mechanisms regulating this process remain poorly understood. Here, we provide evidence that NRG1-ErbB4 signalling functions through the multifunctional scaffold protein, Disrupted in Schizophrenia 1 (DISC1), to regulate the development of cortical inhibitory interneuron dendrite and synaptic growth. We found that NRG1 increases inhibitory neuron dendrite complexity and glutamatergic synapse formation onto inhibitory neurons and that this effect is blocked by expression of a dominant negative DISC1 mutant, or DISC1 knockdown. We also discovered that NRG1 treatment increases DISC1 expression and its localization to glutamatergic synapses being made onto cortical inhibitory neurons. Mechanistically, we determined that DISC1 binds ErbB4 within cortical inhibitory neurons. Collectively, these data suggest that a NRG1-ErbB4-DISC1 signalling pathway regulates the development of cortical inhibitory neuron dendrite and synaptic growth. Given that NRG1, ErbB4, and DISC1 are schizophrenia-linked genes, these findings shed light on how independent risk factors may signal in a common developmental pathway that contributes to neural connectivity defects and disease pathogenesis.

Christensen, Thomas A. and John G. Hildebrand. Coincident stimulation with pheromone components improves temporal pattern resolution in central olfactory neurons. J. Neurophysiol. 77: 775–781, 1997. Male moths must detect and resolve temporal discontinuities in the sex pheromonal odor signal emitted by a conspecific female moth to orient to and locate the odor source. We asked how sensory information about two key components of the pheromone influences the ability of certain sexually dimorphic projection (output) neurons in the primary olfactory center of the male moth's brain to encode the frequency and duration of discrete pulses of pheromone blends. Most of the male-specific projection neurons examined gave mixed postsynaptic responses, consisting of an early suppressive phase followed by activation of firing, to stimulation of the ipsilateral antenna with a blend of the two behaviorally essential pheromone components. Of 39 neurons tested, 33 were excited by the principal (most abundant) pheromone component but inhibited by another, less abundant but nevertheless essential component of the blend. We tested the ability of each neuron to encode intermittent pheromonal stimuli by delivering trains of 50-ms pulses of the two-component blend at progressively higher rates from 1 to 10 per second. There was a strong correlation between 1) the amplitude of the early inhibitory postsynaptic potential evoked by the second pheromone component and 2) the maximal rate of odor pulses that neuron could resolve ( r = 0.92). Projection neurons receiving stronger inhibitory input encoded the temporal pattern of the stimulus with higher fidelity. With the principal, excitatory component of the pheromone alone as the stimulus, the dynamic range for encoding stimulus intermittency was reduced in nearly 60% of the neurons tested. The greatest reductions were observed in those neurons that could be shown to receive the strongest inhibitory input from the second behaviorally essential component of the blend. We also tested the ability of these neurons to encode stimulus duration. Again there was a strong correlation between the strength of the inhibitory input to a neuron mediated by the second pheromone component and that neuron's ability to encode stimulus duration. Neurons that were strongly inhibited by the second component could accurately encode pulses of the blend from 50 to 500 ms in duration ( r = 0.94), but that ability was reduced in neurons receiving little or no inhibitory input ( r = 0.23). This study confirms that certain olfactory projection neurons respond optimally to a particular odor blend rather than to the individual components of the blend. The key components activate opposing synaptic inputs that enable this subset of central neurons to copy the duration and frequency of intermittent odor pulses that are a fundamental feature of airborne olfactory stimuli.