Direct Inhibitory Connections Research Articles

Predictive Neural Computations Support Spoken Word Recognition: Evidence from MEG and Competitor Priming.

Human listeners achieve quick and effortless speech comprehension through computations of conditional probability using Bayes rule. However, the neural implementation of Bayesian perceptual inference remains unclear. Competitive-selection accounts (e.g., TRACE) propose that word recognition is achieved through direct inhibitory connections between units representing candidate words that share segments (e.g., hygiene and hijack share /haidʒ/). Manipulations that increase lexical uncertainty should increase neural responses associated with word recognition when words cannot be uniquely identified. In contrast, predictive-selection accounts (e.g., Predictive-Coding) propose that spoken word recognition involves comparing heard and predicted speech sounds and using prediction error to update lexical representations. Increased lexical uncertainty in words, such as hygiene and hijack, will increase prediction error and hence neural activity only at later time points when different segments are predicted. We collected MEG data from male and female listeners to test these two Bayesian mechanisms and used a competitor priming manipulation to change the prior probability of specific words. Lexical decision responses showed delayed recognition of target words (hygiene) following presentation of a neighboring prime word (hijack) several minutes earlier. However, this effect was not observed with pseudoword primes (higent) or targets (hijure). Crucially, MEG responses in the STG showed greater neural responses for word-primed words after the point at which they were uniquely identified (after /haidʒ/ in hygiene) but not before while similar changes were again absent for pseudowords. These findings are consistent with accounts of spoken word recognition in which neural computations of prediction error play a central role.SIGNIFICANCE STATEMENT Effective speech perception is critical to daily life and involves computations that combine speech signals with prior knowledge of spoken words (i.e., Bayesian perceptual inference). This study specifies the neural mechanisms that support spoken word recognition by testing two distinct implementations of Bayes perceptual inference. Most established theories propose direct competition between lexical units such that inhibition of irrelevant candidates leads to selection of critical words. Our results instead support predictive-selection theories (e.g., Predictive-Coding): by comparing heard and predicted speech sounds, neural computations of prediction error can help listeners continuously update lexical probabilities, allowing for more rapid word identification.

Primate Amygdalo-Nigral Pathway for Boosting Oculomotor Action in Motivating Situations.

SummaryA primary function of the primate amygdala is to modulate behavior based on emotional cues. To study the underlying neural mechanism, we first inactivated the amygdala locally and temporarily by injecting a GABA agonist. Then, saccadic eye movements and gaze were suppressed only on the contralateral side. Next, we performed optogenetic activation after injecting a viral vector into the amygdala. Optical stimulation in the amygdala excited amygdala neurons, whereas optical stimulation of axon terminals in the substantia nigra pars reticulata inhibited nigra neurons. Optical stimulation in either structure facilitated saccades to the contralateral side. These data suggest that the amygdala controls saccades and gaze through the basal ganglia output to the superior colliculus. Importantly, this amygdala-derived circuit mediates emotional context information, whereas the internal basal ganglia circuit mediates object value information. This finding demonstrates a basic mechanism whereby basal ganglia output can be modulated by other areas conveying distinct information.

Complex and spatially segregated auditory inputs of the mouse superior colliculus.

Key points Although the visual circuits in the superior colliculus (SC) have been thoroughly examined, the auditory circuits lack equivalent scrutiny.SC neurons receiving auditory inputs in mice were characterized and three distinguishable types of neurons were found.The auditory pathways from external nuclei of the inferior colliculus (IC) were characterized, and a novel direct inhibitory connection and an excitation that drives feed‐forward inhibitory circuits within the SC were found.The direct excitatory and inhibitory inputs exhibited distinct arbourization patterns in the SC.These findings suggest functional differences between excitatory and inhibitory sensory information that targets the auditory SC. The superior colliculus (SC) is a midbrain structure that integrates auditory, somatosensory and visual inputs to drive orientation movements. While much is known about how visual information is processed in the superficial layers of the SC, little is known about the SC circuits in the deep layers that process auditory inputs. We therefore characterized intrinsic neuronal properties in the auditory‐recipient layer of the SC (stratum griseum profundum; SGP) and confirmed three electrophysiologically defined clusters of neurons, consistent with literature from other SC layers. To determine the types of inputs to the SGP, we expressed Channelrhodopsin‐2 in the nucleus of the brachium of the inferior colliculus (nBIC) and external cortex of the inferior colliculus (ECIC) and optically stimulated these pathways while recording from SGP neurons. Probing the connections in this manner, we described a monosynaptic excitation that additionally drives feed‐forward inhibition via circuits intrinsic to the SC. Moreover, we found a profound long‐range monosynaptic inhibition in 100% of recorded SGP neurons, a surprising finding considering that only about 15% of SGP‐projecting neurons in the nBIC/ECIC are inhibitory. Furthermore, we found spatial differences in the cell body locations as well as axon trajectories between the monosynaptic excitatory and inhibitory inputs, suggesting that these inputs may be functionally distinct. Taking this together with recent anatomical evidence suggesting an auditory excitation from the nBIC and a GABAergic multimodal inhibition from the ECIC, we propose that sensory integration in the SGP is more multifaceted than previously thought.

The rostromedial tegmental nucleus is essential for non-rapid eye movement sleep.

The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep–wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep–wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.

Inhibitory Interneurons Decorrelate Excitatory Cells to Drive Sparse Code Formation in a Spiking Model of V1

Sparse coding models of natural scenes can account for several physiological properties of primary visual cortex (V1), including the shapes of simple cell receptive fields (RFs) and the highly kurtotic firing rates of V1 neurons. Current spiking network models of pattern learning and sparse coding require direct inhibitory connections between the excitatory simple cells, in conflict with the physiological distinction between excitatory (glutamatergic) and inhibitory (GABAergic) neurons (Dale's Law). At the same time, the computational role of inhibitory neurons in cortical microcircuit function has yet to be fully explained. Here we show that adding a separate population of inhibitory neurons to a spiking model of V1 provides conformance to Dale's Law, proposes a computational role for at least one class of interneurons, and accounts for certain observed physiological properties in V1. When trained on natural images, this excitatory-inhibitory spiking circuit learns a sparse code with Gabor-like RFs as found in V1 using only local synaptic plasticity rules. The inhibitory neurons enable sparse code formation by suppressing predictable spikes, which actively decorrelates the excitatory population. The model predicts that only a small number of inhibitory cells is required relative to excitatory cells and that excitatory and inhibitory input should be correlated, in agreement with experimental findings in visual cortex. We also introduce a novel local learning rule that measures stimulus-dependent correlations between neurons to support "explaining away" mechanisms in neural coding.

Inhibitory interneurons enable sparse code formation in a spiking circuit model of V1

Sparse coding accounts for several physiological properties of primary visual cortex (V1), including the shapes of simple cell receptive fields and the highly kurtotic firing rates of V1 neurons [1]. Current spiking network models of pattern learning [2] and sparse coding [3] require direct inhibitory connections between the excitatory simple cells, in violation of Dale's Law which states that neurons can either excite or inhibit but not both. At the same time, the computational role of inhibitory neurons in cortical microcircuit function has yet to be fully explained. Here we show that adding a separate population of inhibitory neurons to a recently proposed model of V1 [3] not only brings spiking network models of sparse coding in line with Dale’s Law, but it also predicts excitatory-to-inhibitory neuron ratios and explains how inhibitory neurons may function computationally. When trained on natural images, this excitatory-inhibitory spiking circuit learns Gabor-like receptive fields as found in V1 using spiking neurons and synaptically local plasticity rules. The inhibitory cells enable sparse code formation using a novel learning rule by collaboratively discovering and suppressing correlations within the excitatory population (Figure ​(Figure1).1). The model predicts that only a small number of inhibitory cells is required relative to excitatory cells, matching physiological ratios observed in primary visual cortex. Figure 1 A. Circuit diagram of our spiking network with separate excitatory (E) and inhibitory (I) neural populations (top) compared to current single population models (bottom). This network was simulated with different numbers of excitatory and inhibitory cells. ...

GABAergic and non-GABAergic spiking interneurons of local and intersegmental groups in the crayfish terminal abdominal ganglion

In the first step toward identifying the neurotransmitter released from spiking interneurons of both local and intersegmental groups in the crayfish terminal abdominal ganglion, the authors examined whether spiking local interneurons and ascending intersegmental interneurons contain the transmitter gamma-aminobutyric acid (GABA). In this paper, 17 identified ascending interneurons and three spiking local interneurons were stained by intracellular injection of Lucifer yellow and subsequently treated for immunocytochemical staining against GABA. Double-labeling experiments revealed that six identified ascending interneurons are GABAergic, but no spiking local interneurons show GABA-like immunoreactivity. Four ascending interneurons with GABA-like immunoreactivity (reciprocal closing ascending neuron 5 [RC-5], reciprocal opening ascending neuron 6 [RO-6], variable-effect ascending interneuron 1 [VE-1], and no-effect ascending interneuron 4[NE-4]) had cell bodies that formed a cluster on the ventral surface of the rostral edge of the ganglion, whereas two GABAergic interneurons (coinhibiting ascending interneuron 2 [CI-2] and NE-2) had cell bodies in a caudal region around the cell body of the seventh flexor inhibitor (FI) motor neuron. Another four rostral interneurons (RC-2, RC-3, RC-4, and NE-3) and seven caudal interneurons (CI-3, RC-7, RO-1, RO-2, RO-3, RO-4, and NE-1) had no GABA-like immunoreactivity. Because VE-1 is known to make direct inhibitory connections with other ascending interneurons, whereas RC-3 and RO-1 are known to make direct excitatory connections, the immunocytochemical results from this study are consistent with previous physiological studies. Although many spiking local interneurons (including spiking local interneuron 1 of the anterior group [sp-ant1]) made direct inhibitory connections with nonspiking local interneurons, three spiking local interneurons (sp-ant1, spiking local interneuron 6 of the medial group [sp-med6], and spiking interneuron 5 of the posterior group [sp-post]) do not show GABA-like immunoreactivity. These results suggest that the inhibitory transmitter released from spiking local interneurons is not GABA but that another substance mediates the inhibitory action of these interneurons. J. Comp. Neurol. 410:677-688.

システムニューロサイエンス教教育講座 ８． 垂直眼球運動の神経機構 垂直性バーストニューロンとその局在

A paramedian area of the mesodiencephalic junction, referred to as the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) or Forel's field H, is important in the genesis of vertical saccadic eye movements. Vertical medium-lead burst neuron (MLBN) exhibits a high frequency burst of spikes that are induced 5-15 msec prior to vertical saccades. These MLBNs are located in the dorsomedial part of the Forel's field H. These MLBNs directly project to the oculomotor nucleus, forming direct synaptic connections with vertical eye movement-related motoneurons in the oculomotor nucleus. Omnipause neurons (OPNs) in the paramedian pontine reticular formation form direct inhibitory connections with vertical MLBNs. Based on these results, we postulated that vertical saccades are generated when the disynaptic excitatory input from the superior colliculus reaches the vertical MLBNs, which form direct connections with vertical motoneurons. The high frequency spike burst of the MLBNs during vertical saccades is presumed to be created by this excitatory input when the MLBNs are released from tonic inhibition caused by OPN activity.

Supra- and juxtatrigeminal inhibitory premotor neurons with bifurcating axons projecting to masseter motoneurons on both sides

Inhibitory neurons participating in the bilateral disynaptic inhibition of jaw-closing motoneurons by stimulation of unilateral trigeminal sensory branches were searched for in the reticular formation around the trigeminal motor nucleus in cats anaesthetized with pentobarbital. Extracellular recordings were made from neurons which responded orthodromically after a monosynaptic latency to single shock stimulation of the ipsilateral infraorbital and/or inferior alveolar nerves. Direct inhibitory connection with contralateral masseter motoneurons was demonstrated in reticular neurons by the spike-triggered averaging technique, i.e., by averaging the intracellular potentials of a contralateral masseter motoneuron with respect to spontaneously occurring spikes of a reticular interneuron. By intraaxonal injection of neurobiotin, electrophysiologically identified inhibitory premotor reticular neurons were found to project to and to terminate in the trigeminal motor nuclei on both sides. Termination in the contralateral motor nucleus was demonstrated for four neurons that showed the peripheral input pattern stated above. The results provide hard evidence for contralaterally projecting interneurons in the reticular formation, participating in peripherally evoked disynaptic inhibition of masseter motoneurons on the contralateral side. Given the previously reported findings that the supratrigeminal region contains neurons which project to the ipsilateral motor nucleus and mediate disynaptic inhibition of masseter motoneurons, it is suggested that the supratrigeminal region contains bilaterally projecting interneurons, mediating peripherally evoked disynaptic inhibition of masseter motoneurons on both sides.

Organization of long-range inhibitory connections with rat visual cortex

We have studied the laminar organization of local long-range inhibitory connections within rat primary visual cortex (area 17) by combining retrograde tracing of nerve cell bodies with glutamic acid decarboxylase immunocytochemistry. While most inhibitory connections are confined to within 0.4 mm of the injection site, a subset of neurons at the layer 5/6 border provide long-range (> 1 mm) inhibitory connections within area 17. However, other cell layers that contain similar local long-range horizontal connections, that is, lower layer 2/3, upper layer 5, and lower layer 6 (Burkhalter and Charles, 1990), show a much more restricted distribution of inhibitory connections. This suggests that cells at the layer 5/6 border play a role in the direct inhibition of neurons at a distant point of the topographic map. Similar double labeling studies reveal long-range inhibitory connections between visual areas. Following injections of fluorescent tracers into area 17, in horizontal sections inhibitory connections can be identified that are up to 8 mm long, linking the extrastriate subdivisions 18a and 18b with striate cortex. Conversely, injections of fluorescent tracers into the cytoarchitectonic subdivision 18a reveal local long-range inhibitory connections within 18a, long-range inhibitory connections between 18a and the cytoarchitectonic subdivision 18b, and inhibitory forward connections from area 17 to 18a. These results suggest that the communication between different cortical areas can be influenced by direct inhibitory connections.

Delayed excitatory connections in the flight system of the locust

1. Synaptic interactions between identified neurons in the flight system of the locust were investigated by the use of standard intracellular recording and staining techniques. The intent was to determine the distribution and functional significance of delayed excitatory connections, which have been previously described. 2. For one inhibitory connection it was demonstrated that subthreshold depolarization of the presynaptic neuron was sufficient to cause release of transmitter at the synapse. This established the existence of graded interactions between spiking flight neurons. 3. Three inhibitory interneurons were found to cause delayed excitatory responses in several other neurons. Often these were coupled with direct inhibitory connections between the same pre- and postsynaptic neurons, resulting in an inhibitory/excitatory (I/E) postsynaptic potential (PSP). The two phases of this PSP were variable. 4. Delayed excitatory connections appeared powerful while the flight system was inactive. However, these connections were disabled during flight rhythms at the phase when the presynaptic neuron was depolarized and firing action potentials. This was likely to be due to the nature of the disynaptic disinhibitory interaction being via (an) intervening neuron(s) with oscillating membrane potentials and thresholds for release of transmitter. 5. Thus connections demonstrated when flight rhythms were not expressed changed their character during flight rhythms. The delayed excitatory connections in this system probably reflect complex circuits of inhibition mediated by graded interactions and have little functional significance as phenomena in their own right.

Cat Pontine Omnipause Neurons: Direct Inhibitory Connection with Forel's Field Burst Neurons Participating in the Genesis of Vertical Saccades

This study investigates synaptic connections of omnipause neurons (OPNs) in the midline pontine tegmentum with vertical medium-lead burst neurons (BNs) in the Forel's field H (FFH), using the microstimulation and spike-triggered averaging techniques in chronically prepared alert cats. OPNs on both sides were antidromically activated by microstimulation at the recording sites of the BNs. Systematic tracking with the stimulating microelectrode revealed indications of profuse axonal branching of OPNs within the BN area. Antidromic spikes of the BNs evoked from the oculomotor nucleus and spike bursts of the BNs associated with saccades were suppressed by OPN area microstimulation. Averaged field potentials in the BN area triggered by spikes of OPNs showed monosynaptic positive waves. These results all but confirm the existence of direct inhibitory synaptic connections of OPNs with the BNs in the FFH. The role of OPNs in the genesis of vertical saccades was also discussed.

Input and output connections of an anteromedial group of spiking local interneurons in the metathoracic ganglion of the locust

Intracellular recordings were made from an anteromedial group of spiking local interneurons in the metathoracic ganglion of the locust to determine the input connections that shape their mechanoreceptive fields on a hindleg and the output connections that define their effects on hindleg motor neurons. The receptive fields of these interneurons may contain excitatory and inhibitory regions. An excitatory region on the ipsilateral hind leg is formed by direct excitatory connections of the afferents from exteroceptors. Afferent spikes consistently evoke EPSPs in interneurons with a central synaptic latency of 1.2-1.5 msec. The connections appear to be direct and chemically mediated. An inhibitory region of a receptive field is not formed by direct afferent connections. Instead, spiking local interneurons of a midline group, which also receive direct excitatory inputs from the afferents, make direct inhibitory connections with anteromedial interneurons. Spikes in particular midline interneurons consistently evoke IPSPs in anteromedial interneurons with a central synaptic latency of about 1.0 msec. The connections appear to be direct and chemically mediated. By contrast, spikes in anteromedial interneurons could not be linked to any synaptic potentials in midline interneurons, so that direct connections are unidirectional and inhibitory. The large inhibitory regions to the receptive fields of anteromedial interneurons result from convergent inhibitory inputs of several midline interneurons. Each midline interneuron may make inhibitory output connections with several anteromedial interneurons, but there is a high degree of specificity in these divergent connections. Anteromedial interneurons make excitatory output connections with specific hind leg motor neurons. EPSPs in motor neurons follow spikes in the interneurons with short and consistent synaptic latencies of about 1.0 msec. The connections appear to be direct and chemically mediated. Two or more anteromedial interneurons with overlapping receptive fields may converge onto one motor neuron, and, in turn, one interneuron may make divergent connections with several motor neurons of the same pool. This pattern of connections suggests that these interneurons are essential elements in the local circuitry responsible for the expression of local reflexes of a leg. They provide an excitatory drive to the motor neurons in parallel to that from nonspiking local interneurons when particular arrays of exteroceptors are stimulated.

Proprioceptive inputs to nonspiking local interneurons contribute to local reflexes of a locust hindleg

Local reflexes of a leg of the locust Schistocerca gregaria (Forskal) can be elicited by selective stimulation of a proprioceptor (the femoral chordotonal organ) at the femorotibial joint. Motor neurons are either excited or inhibited, so that a coordinated reflex response of a leg results. At the same time, some nonspiking local interneurons are either excited or inhibited by the inputs from these proprioceptive afferents. Altering the membrane potential of an individual, nonspiking interneuron can either increase or decrease the response of the participating motor neurons to the proprioceptive stimulus and thereby alter the gain of the reflex. To determine the pathways, and to understand the role of the nonspiking interneurons in mediating these reflex effects, recordings were made simultaneously from these interneurons and afferent neurons. The excitation of a particular nonspiking local interneuron is produced monosynaptically by the afferent neurons. Chemically mediated EPSPs consistently follow sensory spikes with a latency that is the same as that for the known parallel, direct connections made by these sensory neurons with motor neurons (Burrows, 1987a). The chordotonal afferents and the branches of the local interneurons project to the same regions of neuropil. In contrast, the simplest inhibitory pathway is disynaptic, involving spiking local interneurons. The afferents make direct excitatory connections with some of these spiking interneurons, which then make direct inhibitory connections with a nonspiking interneuron. Interactions between the local interneurons add to the complexity of the pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Positive feedback loops from proprioceptors involved in leg movements of the locust

1. Two campaniform sensilla (CS) on the proximal tibia of a hindleg monitor strains set up when a locust prepares to kick, or when a resistance is met during locomotion. The connections made by these afferents with interneurones and leg motor neurones have been investigated and correlated with their role in locomotion. 2. When flexor and extensor tibiae muscles cocontract before a kick afferents from both campaniform sensilla spike at frequencies up to 650 Hz. They do not spike when the tibia is extended actively or passively unless it encounters a resistance. The fast extensor tibiae motor neurone (FETi) then produces a sequence of spikes in a thrusting response with feedback from the CS afferents maintaining the excitation. Destroying the two campaniform sensilla abolishes the re-excitation of FETi. 3. Mechanical stimulation of a single sensillum excites extensor and flexor tibiae motor neurones. The single afferent from either CS evokes EPSPs in the fast extensor motor neurone and in certain fast flexor tibiae motor neurones which follow each sensory spike with a central latency of 1.6 ms that suggests direct connections. The input from one receptor is powerful enough to evoke spikes in FETi. The slow extensor motor neurone does not receive a direct input, although it is excited and slow flexor tibiae motor neurones are unaffected. 4. Some nonspiking interneurones receive direct connections from both afferents in parallel with the motor neurones. One of these interneurones excites the slow and fast extensor tibiae motor neurones probably by disinhibition. Hyperpolarization of this interneurone abolishes the excitatory effect of the CS on the slow extensor motor neurone and reduces the excitation of the fast. The disinhibitory pathway may involve a second nonspiking interneurone with direct inhibitory connections to both extensor motor neurones. Other nonspiking interneurones distribute the effects of the CS afferents to motor neurones of other joints. 5. The branches of the afferents from the campaniform sensilla and those of the motor neurones and interneurones in which they evoke EPSPs project to the same regions of neuropil in the metathoracic ganglion. 6. The pathways described will ensure that more force is generated by the extensor muscle when the tibia is extended against a resistance. The excitatory feedback to the extensor and flexor motor neurones will also contribute to their co-contraction when generating the force necessary for a kick.

Properties of secondary vestibular neurons fired by stimulation of ampullary nerve of the vertical, anterior or posterior, semicircular canals in the cat

Experiments on cats were performed to study the pathway and location of the secondary vestibulo-ocular neurons in response to stimulation of the ampullary nerves of the vertical, anterior or posterior, semicircular canals. Experiments on the medial longitudinal fasciculus transection disclosed that vertical canal-evoked, disynaptic excitation and inhibition were transmitted to the extraocular motoneurons through the contra- and ipsilateral medial longitudinal fasciculus respectively. Secondary vestibular neurons, which receive input from the ampullary nerve of the vertical semicircular canals and send their axons to contralateral medial longitudinal fasciculus, were intermingled in the rostral half of the descending and lateral part of the medial vestibular nuclei. A direct excitatory connection of some of these neurons to the target extraocular motoneurons was confirmed by means of a spike-triggered signal averaging technique. It was also found that neurons activated by antidromic stimulation of ipsilateral medial longitudinal fasciculus were located in the superior vestibular nucleus, some of which made direct inhibitory connections to the target extraocular motoneurons. Both excitatory and inhibitory vestibuloocular neurons made synaptic contact in about half of the impaled target motoneurons.