Role of the human thalamic parafascicular (CM-Pf) complex in neuronal mechanisms of selective attention

Responses of 93 single units of the human thalamic CM-Pf complex to relevant and irrelevant verbal (or sensory) stimuli were studied using microelectrode technique in alert diskinetic patients suffering from the tonic forms of spasmodic torticollis during 11 stereotaxic operations. The response patterns of two types units with irregular unitary (A-type) and low-threshold bursting Ca(2+)-dependent (B-type) spike activity were studied. Three main conclusions emerge from the studies: 1) high reactivity of both A- and B-units to presentation of relevant verbal stimuli with differences of their response patterns as determined by the type of constituent elements; 2) close functional connectivity of these neuronal changes with the level of selective attention; 3) at the moment of attention activation, the appearance of transient interneuronal interactions between adjacent A and B cells characterized by the local synchronization and stabilization of rhythmic oscillations. These data point to considerable contribution of the thalamic CM-Pf complex and its neuronal mechanisms into organization of the human selective attention and triggering verbal-related processing during performance of purposive speech-provoked voluntary acts.     

Significance of local synchronization and oscillatory processes of thalamic neurons in goal-directed human behavior

The time-frequency characteristics and interaction in the cell ensembles of the nonspecific (CM-Pf) and motor (Voi) thalamus were analyzed. Neuronal activity was registered by microelectrode technique during 18 stereotactic neurosurgery operations in spasmodic torticollis patients. The presentation of functionally significant verbal stimuli was accompanied by the emergence of short-term (0.5–1.5 s) local synchronization and stabilization of the oscillatory (3–6 Hz) activity in neighboring neurons of the nonspecific (CM-Pf) thalamus. These focuses of synchronized oscillatory neuronal activity were correlated with the moment of the greatest concentration of selective attention. A similar phenomenon of shortterm synchronization was observed in the motor (Voi) and nonspecific (CM-Pf) thalamus of the human brain during voluntary movements. Synchronization of neuronal activity occurred at the height of the implementation of the motor act, correlating with the maximum muscle tension, as well as in the aftereffect of the voluntary movement. In general, the findings suggest an important role of the local oscillations (3–6 Hz) and synchronization of thalamic neurons in the mechanisms of the relevant information transmission during goal-directed human behavior.     

Neuronal mechanisms of motor signal transmission in the thalamic ventrooral nucleus in spasmodic torticollis patients

A microelectrode technique was used to study the neuronal mechanisms of motor signal transmission in the ventrooral internus nucleus (Voi) of the motor thalamus during voluntary and involuntary pathological (dystonic) movements in patients with spasmodic torticollis. Voi cell elements proved highly reactive to various functional (mostly motor) tests. An activity analysis of 55 Voi neurons detected during nine stereotactic operations revealed, first, a difference in neuronal mechanisms of motor signal transmission for voluntary movements that do or do not involve the affected axial muscles of the neck and for passive and abnormal involuntary dystonic movements. Second, a sensory component was found to play a key role in the mechanisms of sensorimotor interactions during voluntary and involuntary dystonic head and neck movements activating the axial muscles of the neck. Third, rhythmic and synchronized activity of Voi neurons was shown to play an important role in motor signal transmission during voluntary and passive movements. The Voi nucleus was directly implicated in the mechanisms of involuntary head movements and tension of the neck muscles in spasmodic torticollis. The results can be used to identify the Voi nucleus of the thalamus during stereotactic neurosurgery in order to select the optimal destruction or stimulation target and to reduce the postoperative effects in spasmodic torticollis patients.     

Effects of blockade of noradrenergic and serotonergic transmission in theCM-Pf complex on neuronal activity in the motor thalamus in cats

Effects of injections of blockers of the monoaminergic receptor structures into thecentrum medianum-nucl. parafascicularis (CM-Pf) on the activity of neurons in the motor thalamic nuclei (VA-VL) were studied in chronic experiments on awake cats. The animals were trained to perform an operant placing reflex by the forelimb. Injection of a-adrenoblocker, anapriline, into theCM-Pf resulted in enhancement of background activity of neurons of the motor thalamus and facilitation of their spike responses related to conditioned and unconditioned reflex movements. Application of a blocker of serotonin receptors, lysergoamide, evoked opposite changes in the neuronal activity in theVA-VL nuclei: depression of background activity, facilitation of inhibitory processes, and suppression of evoked activity related to conditioned and unconditioned movements. It is supposed that the monoaminergic system of thelocus coeruleus exerts a suppressing influence on the motor thalamus via theCM-Pf complex, while the system of the raphe nuclei facilitates motor thalamic structures.Neirofiziologiya/Neurophysiology, Vol. 28, No. 6, pp. 305–311, November–December, 1996.     

A quantitative comparison of the hominoid thalamus: III. A motor substrate—the ventrolateral complex

Nuclear volumes, nerve cell densities, numbers of neurons, and volumes of nerve cell perikarya of the thalamic ventrolateral complex (VL), a neural substrate for movement, were measured in specimens from two gibbons, one gorilla, one chimpanzee, and three humans, and the values were compared. The human VL had about one-and-a-half times as many neurons as did those of the great apes. The relative frequencies of the sizes of nerve cell perikarya differed slightly in the ventrolateral segment of VL; no differences were noted in the rest of VL. Compared with findings from other parts of the thalamus, the differences in the volumes of VL were greater than those found in the thalamic sensory nuclei, similar to those of rest of the thalamus, and less than those found in the whole brain. The increased number of neurons in human VL was similar to that of the somatosensory relay complex, but greater than those of the auditory and visual nuclei and less than those of the limbic and association nuclei. In human evolution, the numbers of neurons in the VL appeared to increase at a faster rate than did neurons of the pyramidal tract, whereas the motor cortex apparently increased at a rate greater than VL.     

The thalamus in the motor system.

The ventrolateral (VL) and anterior (VA) are the main thalamic relay for cerebellar and pallidal efferents going to the motor cortex. Four aspects of the function of these nuclei are briefly considered. (1) It is well known that these thalamic structures are not a simple relay on the way to the motor cortex, but that they have a gating function for the cerebellar afferents. The gating mechanism is active during slow-wave sleep, with deafferentation and with the use of various anesthetics. Possibly, it might play a role in the central organization of movement. (2) The organization at the unitary level of the projections between VL and motor cortex is examined and their role in the command of motor synergies through the motor cortex is strongly suggested. (3). It appears that unitary activity of VL neurons is not only related to movement but also to postural changes associated with movement. (4) The sensory input to VL nucleus is briefly analyzed. The inefficacy of exteroceptive stimulation in awake animals, in contrast with the effect of the same stimulation in anesthetized preparations, is discussed.     

Efferent connections of the centrum medianum of the cat thalamus revealed by autoradiography

Efferent connections of the centrum medianum and parafascicular nucleus of the thalamus (CM-Pf complex) in cats were studied by the method of anterograde axonal transport of tritiated amino acids followed by autoradiography. Projections from CM-Pf ascend to nuclei of the ventral group and nonspecific nuclei of the thalamus, preoptic, dorsal, lateral, and posterior areas of the hypothalamus, and also into the subthalamic region. Descending pathways are formed only by neurons of the caudomedial part of CM-Pf. They project into the pretectal region, superior colliculus, reticular formation, locus coeruleus, region of the ramus communicans, and substantia grisea centralis of the mesencephalon and pons, and also into the nuclei raphe, magnocellular reticular area, and inferior olivary nucleus of the medulla. In agreement with previous observations it was found that the caudomedial part of CM-Pf does not send direct projections into the cortex and striatum.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 224–230, March–April, 1984.     

Neuronal responses of the reticular and anterior ventral thalamic nuclei to stimulation of the thalamic ventrolateral nucleus and motor cortex

Responses of 137 neurons of the rostral pole of the reticular and anterior ventral thalamic nuclei to electrical stimulation of the ventrolateral nucleus and motor cortex were studied in 17 cats immobilized with D-tubocurarine. The number of neurons responding antidromically to stimulation of the ventrolateral nucleus was 10.5% of all cells tested (latent period of response 0.7–3.0 msec), whereas to stimulation of the motor cortex it was 11.0% (latent period of response 0.4–4.0 msec). Neurons with a dividing axon, one branch of which terminated in the thalamic ventrolateral nuclei, the other in the motor cortex, were found. Orthodromic excitation was observed in 78.9% of neurons tested during stimulation of the ventrolateral nucleus and in 52.5% of neurons during stimulation of the motor cortex. Altogether 55.6% of cells responded to stimulation of the ventrolateral nucleus with a discharge of 3 to 20 action potentials with a frequency of 130–350 Hz. Similar discharges in response to stimulation of the motor cortex were observed in 30.5% of neurons tested. An inhibitory response was recorded in only 6.8% of cells. Convergence of influences from the thalamic ventrolateral nucleus and motor cortex was observed in 55.7% of neurons. The corticofugal influence of the motor cortex on responses arising in these cells to testing stimulation of the ventrolateral nucleus could be either inhibitory or facilitatory.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 10, No. 5, pp. 460–468, September–October, 1978.     

Connections between the anterior thalamic nuclei in turtles (data of the peroxidase method)

It turtles, Testudo horsfieldi (Gray) connections of anterior dorsomedial and dorsolateral thalamic nuclei have been investigated by means of horseradish peroxidase, injected ionophoretically. Retrogradely labelled neurons are predominantly revealed ipsilaterally in the cerebral structures belonging to the limbic system: in the forebrain--basal parts of the hemisphere, septum, adjoining nucleus, nuclei of the anterior and hippocampal commissures, hippocampal cortex, preoptic area; in the diencephalon--in the subthalamus (suprapeduncular nucleus), in some hypothalamic structures (para- and periventricular nuclei, posterior nucleus, lateral hypothalamic area, mamillary complex); in the brain stem--ventral tegmental area, superior nucleus of the suture. Less vast connections are with nonlimbic cerebral formations: projections to the striatum, afferents from the laminar nucleus of the acoustic torus, nuclei of the posterior commissure. Similarity and difference of the nuclei investigated in the turtles with the thalamic anterior nuclei in lizards, with the anterior and intralaminar nuclei in Mammalia are discussed. An idea is suggested on functional heterogeneity of the anterior nuclei in reptiles and on their role for ensuring limbic functions at the thalamic level.     

Characteristics of background unit activity in the nucleus reticularis of the human thalamus

Background firing activity was examined in 240 neurons belonging to the thalamic nucleus reticularis (Rt) in the unanesthetized human brain by extracellular microelectrode recording techniques during stereotaxic surgery for dyskinesia. The cellular organization of Rt was shown to be nonuniform, and distinguished by the presence of three types of neuron: one with arrhythmic single discharge (A-type, 40%), another with rhythmic (2–5 Hz) generation of short high-frequency (of up to 500/sec) burster discharges (B-type, 49%) and a third with aperiodic protracted high-frequency (of up to 500/sec) bursting discharges separated by "silent" intervals of a constant duration of 80–150 msec (i.e., C-type, 11%). Differences between the background activity pattern of these cell types during loss of consciousness under anesthesia are described. Tonic regulation of neuronal type was not pronounced but a tendency was noticed in the cells towards a consistent rise in firing rate, rhythmic frequency and variability, etc. in both A and B units, especially in the latter. Findings pointing to the absence of a direct relationship between rhythmic activity in the Rt and parkinsonian tremor were confirmed. Background activity in B-type cells was found to increase and then stabilize with a rise in the degree of tremor. The nature of regular bursting activity patterns in B and C neurons is discussed in the light of our findings.Institute of Chemical Physics, Academy of Sciences of the USSR, Moscow. Institute of Neurosurgery, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 19, No. 4, pp. 456–466, July–August, 1987.     

Mapping the Effects of SI Cortex Stimulation on Somatosensory Relay Neurons in the Rat Thalamus: Direct Responses and Afferent Modulation

We have used single-unit recording techniques to map the spatial distribution of the primary somatosensory (SI) cortical influences on thalamic somatosensory relay nuclei in the rat. A total of 193 microelectrode penetrations were made to record single neurons in tracks through the medial and lateral ventroposterior (VPL and VPM), ventrolateral (VL), posterior (Po), and reticular (nRt) thalamic nuclei. Single units were classified according to their (1) location within the nuclei, (2) receptive fields, and (3) response to standardized microstimulation in deep layers of the SI cortical forepaw areas. The SI stimulation produced short-latency (1- to 7-msec) excitatory responses in different percentages of neurons recorded in the following thalamic nuclei: VPL, 42.0%; Po, 25.0%; nRt, 16.4%; VL, 13.6%; and VPM, 9.9%. Within the VPL, the highest proportion of responsive neurons was found in the anterior region. Although most of the VL region was unresponsive, the caudal subregion bordering the rostral VPL showed some responsiveness (13.6% of neurons). In general, the spatial pattern of corticothalamic influences appeared to reciprocate the known thalamocortical connection patterns, but with a heterogeneity that was unpredicted.

The same parameters of SI cortical stimulation were used in studies of corticofugal modulation of afferent transmission through the VPL thalamus. A condition—test (C-T) paradigm was implemented in which the cortical stimulation (C) was delivered at a range of time intervals before test (T) mechanical vibratory stimulation was applied to digit 4 of the contralateral forepaw. The time course of cortical effects was analyzed by measuring the averaged evoked unit responses of thalamic neurons to the T stimuli, and plotting them as a function of C-T intervals from 5 to 50 msec. Of the 20 VPL neurons tested during SI stimulation, the average response to T stimulation was decreased a mean of 36%, with the suppression peaking (at 49% inhibition of the afferent response) about 15 msec after the C stimulus. Considerable rostrocaudal variation was observed, however. Whereas neurons in the rostral VPL (near VL) were strongly inhibited (-69%), neurons in the middle and caudal VPL exhibited facilitations at long and short C-T intervals, respectively. This study establishes a specific projection system from the forepaw region of SI cortex to different subregions of the VPL thalamus, producing specific temporal patterns of sensory modulation.     

Mapping the effects of SI cortex stimulation on somatosensory relay neurons in the rat thalamus: direct responses and afferent modulation

We have used single-unit recording techniques to map the spatial distribution of the primary somatosensory (SI) cortical influences on thalamic somatosensory relay nuclei in the rat. A total of 193 microelectrode penetrations were made to record single neurons in tracks through the medial and lateral ventroposterior (VPL and VPM), ventrolateral (VL), posterior (Po), and reticular (nRt) thalamic nuclei. Single units were classified according to their (1) location within the nuclei, (2) receptive fields, and (3) response to standardized microstimulation in deep layers of the SI cortical forepaw areas. The SI stimulation produced short-latency (1- to 7-msec) excitatory responses in different percentages of neurons recorded in the following thalamic nuclei: VPL, 42.0%; Po, 25.0%; nRt, 16.4%; VL, 13.6%; and VPM, 9.9%. Within the VPL, the highest proportion of responsive neurons was found in the anterior region. Although most of the VL region was unresponsive, the caudal subregion bordering the rostral VPL showed some responsiveness (13.6% of neurons). In general, the spatial pattern of corticothalamic influences appeared to reciprocate the known thalamocortical connection patterns, but with a heterogeneity that was unpredicted. The same parameters of SI cortical stimulation were used in studies of corticofugal modulation of afferent transmission through the VPL thalamus. A condition-test (C-T) paradigm was implemented in which the cortical stimulation (C) was delivered at a range of time intervals before test (T) mechanical vibratory stimulation was applied to digit 4 of the contralateral forepaw. The time course of cortical effects was analyzed by measuring the averaged evoked unit responses of thalamic neurons to the T stimuli, and plotting them as a function of C-T intervals from 5 to 50 msec. Of the 20 VPL neurons tested during SI stimulation, the average response to T stimulation was decreased a mean of 36%, with the suppression peaking (at 49% inhibition of the afferent response) about 15 msec after the C stimulus. Considerable rostrocaudal variation was observed, however. Whereas neurons in the rostral VPL (near VL) were strongly inhibited (-69%), neurons in the middle and caudal VPL exhibited facilitations at long and short C-T intervals, respectively. This study establishes a specific projection system from the forepaw region of SI cortex to different subregions of the VPL thalamus, producing specific temporal patterns of sensory modulation.     

Properties of thalamocortical cells identified by antidromic stimulation in the ventrolateral and ventrobasal thalamic nuclei in rats

The physiological and pharmacological properties of thalamocortical neurons, identified by electrical antidromic stimulation of the frontoparietal cortex, were studied in the ventrobasal and ventrolateral thalamic nuclei in urethane anaesthetized rats. The spontaneous activity and conduction velocity of these neurons were similar in both nuclei. At both sites, thalamocortical neurons could be excited through iontophoretic application of acetylcholine and muscarinic or nicotinic agonists. Despite the known differences in thalamic organization of the two species, these properties are quite similar to those described in cat by other authors.     

Role of the basal ganglia in the occurrence of paradoxical sleep dreams (hypothetical mechanism)

A hypothetical mechanism of the basal ganglia involvement in the occurrence of paradoxical sleep dreams and rapid eye movements is proposed. According to this mechanism, paradoxical sleep is provided by facilitation of activation of cholinergic neurons in the pedunculopontine nucleus as a result of suppression of their inhibition from the output basal ganglia nuclei. This disinhibition is promoted by activation of dopaminergic cells by pedunculopontine neurons, subsequent rise in dopamine concentration in the input basal ganglia structure. striatum, and modulation of the efficacy of cortico-striatal inputs. In the absence of signals from retina, a disinhibition of neurons in the pedunculopontine nucleus and superior colliculus allows them to excite neurons in the lateral geniculate body and other thalamic nuclei projecting to the primary and higher visual cortical areas, prefrontal cortex and back into the striatum. Dreams as visual images and "motor hallucinations" are the result of an increase in activity of definitely selected groups of thalamic and neocortical neurons. This selection is caused by modifiable action of dopamine on long-term changes in the efficacy of synaptic transmission during circulation of signals in closed interconnected loops, each of which includes one of the visual cortical areas (motor cortex), one of the thalamic nuclei, limbic and one of the visual areas (motor area) of the basal ganglia. pedunculopontine nucleus, and superior colliculus. Simultaneous modification and modulation of synapses in diverse units of neuronal loops is provided by PGO waves. Disinhibition of superioir colliculus neurons and their excitation by pedunculopontine nucleus lead to an appearance of rapid eye movements during paradoxical sleep.     

Branching-pattern analysis of the dendritic arborization in the thalamic nuclei of the rat brain

We investigated the dendritic patterns of rapid Golgi-impregnated, highly similar multipolar neurons from two functionally different thalamic regions of the rat brain: two dorsal nuclei (the nucleus laterodorsalis thalami, pars dorsomedialis and the nucleus laterodorsalis thalami, pars ventrolateralis), and two ventral nuclei (the nucleus ventrolateralis thalami and the nucleus ventromedialis thalami). The analysis involved conventional morphometric parameters (height and size) and a new parameter derived from graph theory, the relative imbalance (RI), derived from the branching patterns of the dendrites, which permits quantitative characterization of the dendritic arborization of a neuron. On this basis, neurons can be grouped into three fundamentally different types: type A, or highly-polarized (imbalanced) neurons (RI values close to 1); type B, or medium-polarized neurons (RI values around 0.5); and type C, or balanced neurons with low polarization (RI values close to 0). The orientations of the dendritic arbor, and thus the receptive fields, of the dorsal and ventral thalamic neurons, were mutually perpendicular. The H and S values indicated that the neurons in the dorsal and ventral thalamic nuclei differed significantly. However, their RI values demonstrated that they were similar neurons of type B. Our data reveal that 1 ) the dendritic arbor cannot be reliably characterized purely on the basis of height and size, and 2) RI is a valuable morphometric parameter that identifies the true nature of the dendritic arborization.     

A thalamo-cerebral connection in vocal center of canary

Canary song is controlled by two groups of thalamo-cerebral nuclei. One, the hyperstriatum ventrale pars caudale (HVc) and the robust nucleus of the archistriatum (RA), is a motor driving system for vocalization. The other group, which includes the HVc, the nucleus magnocellularis of neostriatum (MAN), Area X and the nucleus dorsointermedius posterior thalami (DIP), modulates the driving system. The HVc receives synaptic projections from the MAN and sends fibers to Area X. Axons of Area X monosynaptically innervate the thalamic nucleus, the DIP, from which neurons extend axons back to the cerebral nucleus, the MAN. DIP neurons relay incoming impulses by way of Area X to the MAN. Double labeling of DIP neurons with HRP and Fast Blue shows that axonal terminals from Area X connect directly with DIP neurons which send fibers to the MAN. The axon formed a bulge from which multiple branches extended to the postsynaptic cell bodies covering most of the surface. The structure of the DIP synapse may be related to a characteristic pattern of discharge of the DIP neuron, which is transmitted over thalamic projection to cerebral vocal nuclei.     

Considerations on the thalamostriatal system with some functional implications

The thalamostriatal projections are largely neglected in current reviews dealing with basal ganglia function. In the past few years, however, several studies have re-evaluated these projections and have postulated their implication in more complex tasks within the basal ganglia organization. In this review, we try to focus on the morphological and functional importance of this system in the basal ganglia of the rat, cat and monkey. Special attention is paid to the thalamus as an important place for interaction between the input and the output systems of the basal ganglia through the thalamostriatal projections. Thus, we stress on the overlapping thalamic territories between the thalamic projection of the output nuclei of the basal ganglia and the thalamostriatal neurons. Our experimental data support the existence of several thalamic feedback circuits within the basal ganglia functional design. Finally, some considerations are provided upon the functional significance of these thalamic feedback circuits in the overall organization of the basal ganglia in health and disease.     

Functional and structural modifications in cells of theVA-VL thalamic nuclei under the influence of the neurotoxin MPTP

We analyzed the peculiarities of interaction between the cerebellar and pallidal effects on the same thalamic neuron observed in intact cats and in cats injected with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as well as ultrastructural changes, which develop in the motor thalamic neurons affected by this toxin. Responses of 225 neurons of the ventral anterior (VA) and ventral lateral (VL) thalamic nuclei were studied in intact animals, and 218 neurons of these nuclei were recorded in MPTP-treated cats. Nerve cells responding to stimulation of both cerebellar and pallidal inputs constituted 7–8% of all neurons under study; they were mostly localized in the medialVA-VL regions. In the norm, conditioning stimulation of the pallidum was accompanied in 68% of the cases by complete inhibition of neuronal responses to test stimulation of cerebellar fibers (at 1- to 6-msec-long interstimulus intervals). After a 5-day-long course of MPTP injections, conditioning pallidal stimulation-induced inhibition of test responses was observed in a much smaller share of the cases (27%). Such a drop in the efficacy of pallidal inhibitory influences may be related to MPTP-induced structural modifications of the pallido-thalamic synapses. Electron microscopic examination showed that MPTP treatment resulted in the development of ultrastructural manifestations of hydropic dystrophy and clearly expressed depletion of synaptic vesicles in the F1-type synapses distributed on the dendrites of thalamo-corticalVA-VL neurons (these synapses, according to their structural features, were identified as pallido-thalamic contacts). A decrease in the dimension of axon terminals and intensified osmium staining of the synaptoplasm were also observed.     

Spatial organization of neurons in the dorsal motor nucleus of the vagus synapsing with intragastric cholinergic and nitric oxide/VIP neurons in the rat

The dorsal motor nucleus of the vagus (DMV) contains preganglionic neurons that control gastric motility and secretion. Stimulation of different parts of the DMV results in a decrease or an increase in gastric motor activities, suggesting a spatial organization of vagal preganglionic neurons in the DMV. Little is known about how these preganglionic neurons in the DMV synapse with different groups of intragastric motor neurons to mediate contraction or relaxation of the stomach. We used pharmacological and immunohistochemical methods to characterize intragastric neural pathways involved in mediating gastric contraction and relaxation in rats. Microinjections of L-glutamate (L-Glu) into the rostral or caudal DMV produced gastric contraction and relaxation, respectively, in a dose-related manner. Intravenous infusion of hexamethonium blocked these actions, suggesting mediation via preganglionic cholinergic pathways. Atropine inhibited gastric contraction by 85.5 +/- 4.5%. Gastric relaxation was reduced by intravenous administration of N(G)-nitro-L-arginine methyl ester (L-NAME; 52.5 +/- 11.9%) or VIP antagonist (56.3 +/- 14.9%). Combined administration of L-NAME and VIP antagonist inhibited gastric relaxation evoked by L-Glu (87.8 +/- 4.3%). Immunohistochemical studies demonstrated choline acetyltransferase immunoreactivity in response to L-Glu microinjection into the rostral DMV in 88% of c-Fos-positive intragastric myenteric neurons. Microinjection of L-Glu into the caudal DMV evoked expression of nitric oxide (NO) synthase and VIP immunoreactivity in 81 and 39%, respectively, of all c-Fos-positive intragastric myenteric neurons. These data indicate spatial organization of the DMV. Depending on the location, microinjection of L-Glu into the DMV may stimulate intragastric myenteric cholinergic neurons or NO/VIP neurons to mediate gastric contraction and relaxation.     

Multiple neural oscillators and muscle feedback are required for the intestinal fed state motor program

After a meal, the gastrointestinal tract exhibits a set of behaviours known as the fed state. A major feature of the fed state is a little understood motor pattern known as segmentation, which is essential for digestion and nutrient absorption. Segmentation manifests as rhythmic local constrictions that do not propagate along the intestine. In guinea-pig jejunum in vitro segmentation constrictions occur in short bursts together with other motor patterns in episodes of activity lasting 40-60 s and separated by quiescent episodes lasting 40-200 s. This activity is induced by luminal nutrients and abolished by blocking activity in the enteric nervous system (ENS). We investigated the enteric circuits that regulate segmentation focusing on a central feature of the ENS: a recurrent excitatory network of intrinsic sensory neurons (ISNs) which are characterized by prolonged after-hyperpolarizing potentials (AHPs) following their action potentials. We first examined the effects of depressing AHPs with blockers of the underlying channels (TRAM-34 and clotrimazole) on motor patterns induced in guinea-pig jejunum, in vitro, by luminal decanoic acid. Contractile episode durations increased markedly, but the frequency and number of constrictions within segmenting bursts and quiescent period durations were unaffected. We used these observations to develop a computational model of activity in ISNs, excitatory and inhibitory motor neurons and the muscle. The model predicted that: i) feedback to ISNs from contractions in the circular muscle is required to produce alternating activity and quiescence with the right durations; ii) transmission from ISNs to excitatory motor neurons is via fast excitatory synaptic potentials (EPSPs) and to inhibitory motor neurons via slow EPSPs. We conclude that two rhythm generators regulate segmentation: one drives contractions within segmentation bursts, the other the occurrence of bursts. The latter depends on AHPs in ISNs and feedback to these neurons from contraction of the circular muscle.