Ventroposterior Medial Thalamus Research Articles

Orally administered oxytocin alters brain activation and behaviors of pre-weaning mice

Oxytocin (OXT) regulates adult social behavior and has been implicated in its development. Because mammalian milk contains OXT and we have recently identified OXT receptors (OXTR) in the face and oronasal cavity of pre-weaning mice, we hypothesize that orally applied OXT may impact brain activity and acute behavior in developing mice. Oral OXT may have effects in the absence of sensory stimulation or perhaps by modulating sensory input, such as whisker stimulation. The present study investigates the acute c-Fos response in the paraventricular nucleus of the hypothalamus (PVN) and along whisker sensory processing brain regions (trigeminothalamocortical circuit) to orally applied OXT, compared to saline, with and without whisker stimulation in postnatal day (P) 14 and P21 male and female mice. Acute behavioral responses were also quantified after oral OXT with whisker stimulation in a non-social context. Oral OXT with and without whisker stimulation increased c-Fos activity in the PVN of males and decreased c-Fos in the ventroposterior medial thalamus in both males and females compared to saline. Additionally, oral OXT with whisker stimulation decreased c-Fos activity across whisker sensory processing brain regions in males and females and decreased c-Fos activity in the trigeminal motor nucleus of females. Lastly, oral OXT with whisker stimulation increased males' locomotor behavior and decreased females' oromotor behavior compared to saline-treated controls. These data indicate that orally applied OXT has acute brain and behavioral effects on developing mice. OXT-modulated sensory signals may bias brain and behavior development toward the social world.

Primary Tactile Thalamus Spiking Reflects Cognitive Signals.

Little is known about whether information transfer at primary sensory thalamic nuclei is modified by behavioral context. Here we studied the influence of previous decisions/rewards on current choices and preceding spike responses of ventroposterior medial thalamus (VPm; the primary sensory thalamus in the rat whisker-related tactile system). We trained head-fixed rats to detect a ramp-like deflection of one whisker interspersed within ongoing white noise stimulation. Using generative modeling of behavior, we identify two task-related variables that are predictive of actual decisions. The first reflects task engagement on a local scale ("trial history": defined as the decisions and outcomes of a small number of past trials), whereas the other captures behavioral dynamics on a global scale ("satiation": slow dynamics of the response pattern along an entire session). Although satiation brought about a slow drift from Go to NoGo decisions during the session, trial history was related to local (trial-by-trial) patterning of Go and NoGo decisions. A second model that related the same predictors first to VPm spike responses, and from there to decisions, indicated that spiking, in contrast to behavior, is sensitive to trial history but relatively insensitive to satiation. Trial history influences VPm spike rates and regularity such that a history of Go decisions would predict fewer noise-driven spikes (but more regular ones), and more ramp-driven spikes. Neuronal activity in VPm, thus, is sensitive to local behavioral history, and may play an important role in higher-order cognitive signaling.SIGNIFICANCE STATEMENT It is an important question for perceptual and brain functions to find out whether cognitive signals modulate the sensory signal stream and if so, where in the brain this happens. This study provides evidence that decision and reward history can already be reflected in the ascending sensory pathway, on the level of first-order sensory thalamus. Cognitive signals are relayed very selectively such that only local trial history (spanning a few trials) but not global history (spanning an entire session) are reflected.

Efficient population coding of naturalistic whisker motion in the ventro-posterior medial thalamus based on precise spike timing

The rodent whisker-associated thalamic nucleus (VPM) contains a somatotopic map where whisker representation is divided into distinct neuronal sub-populations, called “barreloids”. Each barreloid projects to its associated cortical barrel column and so forms a gateway for incoming sensory stimuli to the barrel cortex. We aimed to determine how the population of neurons within one barreloid encodes naturalistic whisker motion. In rats, we recorded the extracellular activity of up to nine single neurons within a single barreloid, by implanting silicon probes parallel to the longitudinal axis of the barreloids. We found that play-back of texture-induced whisker motion evoked sparse responses, timed with millisecond precision. At the population level, there was synchronous activity: however, different subsets of neurons were synchronously active at different times. Mutual information between population responses and whisker motion increased near linearly with population size. When normalized to factor out firing rate differences, we found that texture was encoded with greater informational-efficiency than white noise. These results indicate that, within each VPM barreloid, there is a rich and efficient population code for naturalistic whisker motion based on precisely timed, population spike patterns.

A bundled microwire array for long-term chronic single-unit recording in deep brain regions of behaving rats

Chronic single-unit recording in subcortical brain regions is increasingly important in neurophysiological studies. However, methods for long-term, stable recording of multiple single-units in deep brain regions and in dura-surrounded ganglion have not yet been established. In the present study, we propose a bundled microwire array design which is capable of long-term recording of the trigeminal ganglion and deep-brain units. This electrode set is easy to construct from common materials and tools found in an electrophysiological laboratory. The salient features of our design include: (1) short and separated tungsten microwires for stable chronic recording; (2) the use of a 30-guage stainless steel guide tube for facilitating penetration and aiming for deep targets as well as electrical grounding; (3) the inclusion of a reference of the same microwire material inside the bundle to enhance common mode rejection of far field noises; and (4) an adjustable connector. In our case, we used a 90° backward bending connector so that implanted rats could perform the same hole-seeking behavior and their faces and the whiskers could be stimulated in the behaving state. It was demonstrated that this multi-channel electrode caused minimal tissue damage at the recording site and we were able to obtain good, stable single-unit recordings from the trigeminal ganglion and ventroposterior medial thalamus areas of freely moving rats for up to 80 days. This methodology is useful for the studies that require long term and high quality unit recording in the deep brain or in the trigeminal system.

Thalamic morphology in schizophrenia and schizoaffective disorder

Background Biomarkers are needed that can distinguish between schizophrenia and schizoaffective disorder to inform the ongoing debate over the diagnostic boundary between these two disorders. Neuromorphometric abnormalities of the thalamus have been reported in individuals with schizophrenia and linked to core features of the disorder, but have not been similarly investigated in individuals with schizoaffective disorder. In this study, we examine whether individuals with schizoaffective disorder have a pattern of thalamic deformation that is similar or different to the pattern found in individuals with schizophrenia. Method T1-weighted magnetic resonance images were collected from individuals with schizophrenia ( n = 47), individuals with schizoaffective disorder ( n = 15), and controls ( n = 42). Large-deformation, high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance were used to test for group differences in volume and measures of surface shape. Results Individuals with schizophrenia or schizoaffective disorder have similar thalamic volumes. Thalamic surface shape deformation associated with schizophrenia suggests selective involvement of the anterior and posterior thalamus, while deformations in mediodorsal and ventrolateral regions were observed in both groups. Schizoaffective disorder had distinct deformations in medial and lateral thalamic regions. Conclusions Abnormalities distinct to schizoaffective disorder suggest involvement of the central and ventroposterior medial thalamus which may be involved in mood circuitry, dorsolateral nucleus which is involved in recall processing, and the lateral geniculate nucleus which is involved in visual processing.

Transformation in the neural code for whisker deflection direction along the lemniscal pathway.

A prominent characteristic of neurons in the whisker system is their selectivity to the direction in which a whisker is deflected. The aim of this study was to determine how information about whisker direction is encoded at successive levels of the lemniscal pathway. We made extracellular recordings under identical conditions from the trigeminal ganglion, ventro-posterior medial thalamus (VPM), and barrel cortex while varying the direction of whisker deflection. We found a marked increase in the variability of single unit responses along the pathway. To study the consequences of this for information processing, we quantified the responses using mutual information. VPM units conveyed 48% of the mutual information conveyed by ganglion units, and cortical units conveyed 12%. The fraction of neuronal bandwidth used for transmitting direction information decreased from 40% in the ganglion to 24% in VPM and 5% in barrel cortex. To test whether, in cortex, population coding might compensate for this information loss, we made simultaneous recordings. We found that cortical neuron pairs conveyed 2.1 times the mutual information conveyed by single neurons. Overall, these findings indicate a marked transformation from a subcortical neural code based on small numbers of reliable neurons to a cortical code based on populations of unreliable neurons. However, the basic form of the neural code in ganglion, thalamus, and cortex was similar-at each stage, the first poststimulus spike carried the majority of the information.

Cortical Transformation of Wide-Field (Multiwhisker) Sensory Responses

In the barrel cortex of rodents, cells respond to a principal whisker (PW) and more weakly to several adjacent whiskers (AWs). Here we show that compared with PW responses, simultaneous wide-field stimulation of the PW and several AWs enhances short-latency responses and suppresses long-latency responses. Multiwhisker enhancement and suppression is first seen at the level of the cortex in layer 4 and not in the ventroposterior medial thalamus. Within the cortex, enhancement is manifested as a reduction in spike latency in layer 4 but also as an increase in spike probability in layer 2/3. Intracellular recordings revealed that multiwhisker enhancement of short-latency responses is caused by synaptic summation that can be explained by synaptic cooperativity (i.e., convergence of synaptic inputs activated by different whiskers). Conversely, multiwhisker suppression of long-latency responses is due to increased recruitment of inhibition in cortical cells. Interestingly, the ability to differentiate multiwhisker and PW responses is lost during rapid sensory adaptation caused by high-frequency whisker stimulation. The results reveal that simultaneous and temporally dispersed wide-field sensory inputs are discriminated at the level of single cells in barrel cortex with high temporal resolution, but the ability to compute this difference is highly dynamic and dependent on the level of adaptation in the thalamocortical network.

Noradrenergic Activation Amplifies Bottom-Up and Top-Down Signal-to-Noise Ratios in Sensory Thalamus

Thalamocortical cells receive sensory signals via primary sensory afferents and cortical signals via corticothalamic afferents. These signals are influenced by a variety of neuromodulators that are released in the thalamus during specific behavioral states. Hence, different neuromodulators may set different thalamic modes of sensory information processing. We found that noradrenergic activation affects sensory and corticothalamic signals in the whisker thalamus differently than cholinergic activation. Whereas cholinergic activation increases the spontaneous firing (noise) and enlarges the receptive fields of ventroposterior medial thalamus (VPM) cells, noradrenergic activation decreases spontaneous firing and focuses receptive fields. Consequently, for sensory signals, noradrenergic activation sets bottom-up thalamic processing to a focused and noise-free excitatory receptive field, which contrasts with the broad and noisy excitatory receptive field characteristic of cholinergic activation. For corticothalamic signals, noradrenergic activation sets top-down processing to a noise-free high-frequency signal detection mode, whereas cholinergic activation produces a noisy broadband signal detection mode. The effects of noradrenergic activation on signal-to-noise ratios of VPM cells were found to be mediated by nucleus reticularis thalamic (nRt) cells. Hence, a major role of nRt cells is to regulate the noise level of thalamocortical cells during sensory processing. In conclusion, different modulators establish distinct modes of bottom-up and top-down information processing in the sensory thalamus.

Spatiotemporal Gating of Sensory Inputs in Thalamus during Quiescent and Activated States

The main role of the thalamus is to relay sensory inputs to the neocortex according to the regulations dictated by behavioral state. Hence, changes in behavioral state are likely to transform the temporal and spatial properties of thalamocortical receptive fields. We compared the receptive fields of single cells in the ventroposterior medial thalamus (VPM) of urethane-anesthetized rats during quiescent states and during aroused (activated) states. During quiescent states, VPM cells respond to stimulation of a principal whisker (PW) and may respond modestly to one or a few adjacent whiskers (AWs). During either generalized forebrain activation or selective thalamic activation caused by carbachol infusion in the VPM, the responses to AWs enhance so that VPM receptive fields become much larger. Such enlargement is not observed at the level of the principal trigeminal nucleus, indicating that it originates within the thalamus. Interestingly, despite the increase in AW responses during activation, simultaneous deflection of the PW and AWs produced VPM responses that resembled the PW response, as if the AWs were not stimulated. This nonlinear summation of sensory responses was present during both quiescent and activated states. In conclusion, the thalamus suppresses the excitatory surround (AWs) of the receptive field during quiescent states and enlarges this surround during arousal. But, thalamocortical cells represent only the center (PW) of the receptive field when the center (PW) and surround (AWs) are stimulated simultaneously.

Coding of Stimulus Frequency by Latency in Thalamic Networks Through the Interplay of GABAB-Mediated Feedback and Stimulus Shape

A temporal sensory code occurs in posterior medial (POm) thalamus of the rat vibrissa system, where the latency for the spike rate to peak is observed to increase with increasing frequency of stimulation between 2 and 11 Hz. In contrast, the latency of the spike rate in the ventroposterior medial (VPm) thalamus is constant in this frequency range. We consider the hypothesis that two factors are essential for latency coding in the POm. The first is GABAB-mediated feedback inhibition from the reticular thalamic (Rt) nucleus, which provides delayed and prolonged input to thalamic structures. The second is sensory input that leads to an accelerating spike rate in brain stem nuclei. Essential aspects of the experimental observations are replicated by the analytical solution of a rate-based model with a minimal architecture that includes only the POm and Rt nuclei, i.e., an increase in stimulus frequency will increase the level of inhibitory output from Rt thalamus and lead to a longer latency in the activation of POm thalamus. This architecture, however, admits period-doubling at high levels of GABAB-mediated conductance. A full architecture that incorporates the VPm nucleus suppresses period-doubling. A clear match between the experimentally measured spike rates and the numerically calculated rates for the full model occurs when VPm thalamus receives stronger brain stem input and weaker GABAB-mediated inhibition than POm thalamus. Our analysis leads to the prediction that the latency code will disappear if GABAB-mediated transmission is blocked in POm thalamus or if the onset of sensory input is too abrupt. We suggest that GABAB-mediated inhibition is a substrate of temporal coding in normal brain function.

Immediate thalamic sensory plasticity depends on corticothalamic feedback.

Multiple neuron ensemble recordings were obtained simultaneously from both the primary somatosensory (SI) cortex and the ventroposterior medial thalamus (VPM) before and during the combined administration of reversible inactivation of the SI cortex and a reversible subcutaneous block of peripheral trigeminal nerve fibers. This procedure was performed to quantify the contribution of descending corticofugal projections on (i) the normal organization of thalamic somatosensory receptive fields and (ii) the thalamic somatosensory plastic reorganization that immediately follows a peripheral deafferentation. Reversible inactivation of SI cortex resulted in immediate changes in receptive field properties throughout the VPM. Cortical inactivation also significantly reduced but did not completely eliminate the occurrence of VPM receptive field reorganization resulting from the reversible peripheral deafferentation. This result suggests that the thalamic plasticity that is seen immediately after a peripheral deafferentation is dependent upon both descending corticofugal projections and ascending trigeminothalamic projections.

Local circuit in the cerebral cortex: Inputs to corticospinal projection neurons

The utility of extracellular microstimulation as an ancillary tool to compliment cross-correlation analyses is explored. This technique aims at demonstrating the ‘sufficiency’ of the spike train generated by the ‘reference’ neuron in eliciting spikes in the ‘target’ neuron. It involves activating the reference neuron with very low-intensity current pulses (1–10 μA) delivered through the recording microelectrode. Microstimulation can provide independent evidence that can either support or refute notions of synaptic connectivity generated by correlation analyses. Data are presented from antidromically identified descending corticofugal neurons and putative inhibitory interneurons of S1 ‘barrel’ cortex of the rabbit and from simultaneously recorded neurons in the topographically aligned ‘barreloid’ of ventroposterior medial thalamus (VPM). A very strong relationship was seen between brief, statistically significant peaks in the cross-correlograms (CCGs) suggestive of monosynaptic excitatory input and the responses of cortical neurons to VPM microstimulation. Thus, 1819 cortical neurons that responded to microstimulation pulses of < 6 μA showed a significant CCG with the VPM neuron. Conversely, each of 16 cortical neurons that failed to respond at 10 μA also failed to show a significant CCG. CCGs compiled from independent data sets collected before and after hundreds of microstimulation pulses were very similar, showing that such stimulation can be relatively benign. The method has many limitations, which are discussed. The most serious problem is that the effects of extracellular current pulses cannot be limited to the reference neuron. Nevertheless, microstimulation can provide independent experimental support or refutation of hypotheses of synaptic connectivity that are generated by cross-correlation analyses. In addition, since the technique is rapidly implemented and has considerable power to predict significant cross-correlations, it can be useful in deciding which neuron pairs to study when limited time is available for data collection.

Cross-correlation and microstimulation: complementary tools in the extracellular analysis of synaptic interactions

The utility of extracellular microstimulation as an ancillary tool to compliment cross-correlation analyses is explored. This technique aims at demonstrating the ‘sufficiency’ of the spike train generated by the ‘reference’ neuron in eliciting spikes in the ‘target’ neuron. It involves activating the reference neuron with very low-intensity current pulses (1–10 μA) delivered through the recording microelectrode. Microstimulation can provide independent evidence that can either support or refute notions of synaptic connectivity generated by correlation analyses. Data are presented from antidromically identified descending corticofugal neurons and putative inhibitory interneurons of S1 ‘barrel’ cortex of the rabbit and from simultaneously recorded neurons in the topographically aligned ‘barreloid’ of ventroposterior medial thalamus (VPM). A very strong relationship was seen between brief, statistically significant peaks in the cross-correlograms (CCGs) suggestive of monosynaptic excitatory input and the responses of cortical neurons to VPM microstimulation. Thus, 18 19 cortical neurons that responded to microstimulation pulses of < 6 μA showed a significant CCG with the VPM neuron. Conversely, each of 16 cortical neurons that failed to respond at 10 μA also failed to show a significant CCG. CCGs compiled from independent data sets collected before and after hundreds of microstimulation pulses were very similar, showing that such stimulation can be relatively benign. The method has many limitations, which are discussed. The most serious problem is that the effects of extracellular current pulses cannot be limited to the reference neuron. Nevertheless, microstimulation can provide independent experimental support or refutation of hypotheses of synaptic connectivity that are generated by cross-correlation analyses. In addition, since the technique is rapidly implemented and has considerable power to predict significant cross-correlations, it can be useful in deciding which neuron pairs to study when limited time is available for data collection.

Influence of VPM afferents on putative inhibitory interneurons in S1 of the awake rabbit: evidence from cross-correlation, microstimulation, and latencies to peripheral sensory stimulation.

1. Responses of thalamocortical projection neurons and suspected cortical interneurons (SINs) to very brief peripheral stimuli were examined within the vibrissae, the sinus hair, the lip, and the chin representations of ventroposterior medial thalamus (VPM) and primary somatosensory cortex (S1). VPM thalamocortical neurons (N = 40) were identified by their antidromic activation after electrical stimulation of S1. SINs were identified by a high-frequency (> 600 Hz) burst of three or more spikes elicited by suprathreshold stimulation of one or more afferent pathways. SINs also had spikes of very short duration. 2. Previous work has shown that electrical stimulation of VPM elicits a very early and powerful synaptic response in many S1 SINs. Three experimental strategies were employed to test the hypothesis that such responses reflect a monosynaptic VPM input onto SINs and to examine the effects of such input. 1) After a brief peripheral stimulus, the arrival times of VPM thalamocortical impulses in S1 were determined and compared with the initial response times of S1 SINs. 2) Shift-corrected cross-correlograms (CCGs) were constructed from the spike trains of pairs of VPM neurons and SINs that were in precise topographic alignment. 3) Inferences of connectivity based on such CCGs were supported by applying very low-intensity (1-10 microA) microstimulation pulses to the recording microelectrode in VPM and observing evoked responses in the cortical SIN. 3. VPM thalamocortical neurons responded to a brief air puff stimulus at a median latency of 5.05 ms, and the estimated arrival time of the VPM impulses at S1 had a median value of 5.97 ms. This estimate was obtained by adding the antidromic latency of each VPM neuron to the latency of the peripheral stimulus and was supported by similar values obtained from three VPM thalamocortical axons recorded near their termination site within S1. SINs of S1 were among the first cortical neurons to respond to the peripheral stimulus, responding to the air puff at a median latency of 6.6 ms (range 5.7-13.0 ms). The latency of SINs to the peripheral stimulus was strongly related to the latency to gross electrical stimulation of VPM (median value 1.52 ms, r2 = +0.44, P < 0.0001). Many SINs (23 of 34) showed significant shift-corrected CCGs with VPM neurons that were in precise topographic alignment. Most significant CCGs revealed a very brief increase in SIN spike probability (half-amplitude response of approximately 1 ms) that reached a peak value at intervals of 1.4-2.0 ms after the VPM spike.(ABSTRACT TRUNCATED AT 400 WORDS)

Localization of glutamate in trigeminothalamic projection neurons: a combined retrograde transport-immunohistochemical study.

Trigeminothalamic projection neurons are important components of the pathways for conscious perception of pain, temperature, and tactile sensation from the orofacial region. The neurotransmitters utilized by trigeminal neurons projecting to the thalamus are unknown. By use of a monoclonal antibody specific for fixative-modified glutamate and a polyclonal antiserum against glutaminase, we recently identified neurons in the trigeminal sensory complex that contain glutamate-like immunoreactivity (Glu-LI) and glutaminase-like immunoreactivity. In the present study, we utilized combined retrograde transport-immunohistochemical techniques to localize putative glutamatergic trigeminothalamic neurons. Following injection of the retrograde tracer, wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP), into the ventroposterior medial thalamus (VPM), the number of neuronal profiles that were double-labeled with WGA:HRP and Glu-LI was greatest in principal sensory nucleus (Pr5), followed by subnuclei interpolaris (Sp5I) and caudalis (Sp5C). The average percentages of projection neurons double-labeled with Glu-LI were approximately 60-70% in Pr5 and Sp5I and 40% in Sp5C. The majority of double-labeled profiles in Sp5C were located in the magnocellular layer, as opposed to the marginal and substantia gelatinosa layers. A large injection site that spread into the intralaminar thalamic nuclei and nucleus submedius--areas implicated in the processing of nociceptive information--resulted in an increase in the ratio of single-labeled to double-labeled projection profiles in Sp5C. These results suggest that glutamate may be the neurotransmitter for a majority of trigeminothalamic projection neurons located in Sp5I and Pr5. However, on the basis of anatomical association, glutamate does not appear to be the major transmitter for neurons in Sp5C that forward nociceptive information to the thalamus.

Birthweight between 14 and 42 weeks' gestation.

Data representing fetal weight gain between 14 and 42 weeks' gestation are presented; firstly to provide suitable curves enabling the growth of the very immature infant to be monitored and secondly to examine the influence of the improved techniques of paediatric and obstetric assessment developed since the publication of previous studies. Data have been collected from the 57 866 livebirths in Sheffield between 1976 and 1984 and from therapeutically terminated and spontaneously aborted fetuses over the same period. It seems that preterm livebirths do not form a different population with respect to weight from the fetus still in utero, at least until the beginning of the third trimester. Previous studies have reported a bimodality of weight distribution in preterm infants at each gestational age which has been attributed to errors in gestational assessment. The pattern of distribution of weight in this study suggests that early ultrasonography and paediatric assessment techniques have exerted a considerable influence on the accuracy of gestational assessment. The mean weights of the sample differ considerably from those of the Gairdner and Pearson chart which are, therefore, considered to be inappropriate for the Sheffield population.