[Show abstract][Hide abstract] ABSTRACT: Stimulus-specific adaptation (SSA) is observed in many brain regions in humans and animals. SSA of cortical neurons has been proposed to accumulate through relays in ascending pathways. Here, we examined SSA at the synapse level using whole-cell patch-clamp recordings of primary cultured cortical neurons of the rat. First, we found that cultured neurons had high firing capability with 100-Hz current injection. However, neuron firing started to adapt to repeated electrically activated synaptic inputs at 10 Hz. Next, to activate different dendritic inputs, electrical stimulations were spatially separated. Cultured neurons showed similar SSA properties in the oddball stimulation paradigm compared to those reported in vivo. Single neurons responded preferentially to a deviant stimulus over repeated, standard stimuli considering both synapse-driven spikes and excitatory postsynaptic currents (EPSCs). Compared with two closely placed stimulating electrodes that activated highly overlapping dendritic fields, two separately placed electrodes that activated less overlapping dendritic fields elicited greater SSA. Finally, we used glutamate puffing to directly activate postsynaptic glutamate receptors. Neurons showed SSA to two separately placed puffs repeated at 10 Hz. Compared with EPSCs, GABAa receptor-mediated inhibitory postsynaptic currents showed weaker SSA. Heterogeneity of the synaptic inputs was critical for producing SSA, with glutamate receptor desensitization participating in the process. Our findings suggest that postsynaptic fatigue contributes largely to SSA at low frequencies.
PLoS ONE 12/2014; 9(12):e114537. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Freezing rate minimized in the first two weeks after training when the EC inactivated.•Retrieval of new associative fear memory depended on the entorhinal cortex (EC).•Fear memory extinguished over 4 to 5 weeks.•Dependence of fear memory retrieval on the EC decreased over 4 to 5 weeks.
Neurobiology of Learning and Memory 11/2014; · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A brain-machine interface (BMI) is a neuroprosthetic device that can restore motor function of individuals with paralysis. Although the feasibility of BMI control of upper-limb neuroprostheses has been demonstrated, a BMI for the restoration of lower-limb motor functions has not yet been developed. The objective of this study was to determine if gait-related information can be captured from neural activity recorded from the primary motor cortex of rats, and if this neural information can be used to stimulate paralysed hindlimb muscles after complete spinal cord transection. Neural activity was recorded from the hindlimb area of the primary motor cortex of six female Sprague Dawley rats during treadmill locomotion before and after mid-thoracic transection. Before spinal transection there was a strong association between neural activity and the step cycle. This association decreased after spinal transection. However, the locomotive state (standing vs. walking) could still be successfully decoded from neural recordings made after spinal transection. A novel BMI device was developed that processed this neural information in real-time and used it to control electrical stimulation of paralysed hindlimb muscles. This system was able to elicit hindlimb muscle contractions that mimicked forelimb stepping. We propose this lower-limb BMI as a future neuroprosthesis for human paraplegics.
PLoS ONE 08/2014; 9(8):e103764. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The ability to detect unexpected or deviant events in natural scenes is critical for survival. In the auditory system, neurons from the midbrain to cortex adapt quickly to repeated stimuli but this adaptation does not fully generalize to other rare stimuli, a phenomenon called stimulus-specific adaptation (SSA). Most studies of SSA were conducted with pure tones of different frequencies, and it is by now well-established that SSA to tone frequency is strong and robust in auditory cortex. Here we tested SSA in the auditory cortex to the ear of stimulation using broadband noise. We show that cortical neurons adapt specifically to the ear of stimulation, and that the contrast between the responses to stimulation of the same ear when rare and when common depends on the binaural interaction class of the neurons.
Frontiers in Neural Circuits 07/2014; 8:89. · 2.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements.
Journal of NeuroEngineering and Rehabilitation 07/2014; 11(1):107. · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex.Cell Research advance online publication 17 December 2013; doi:10.1038/cr.2013.164.
[Show abstract][Hide abstract] ABSTRACT: Damage to the medial temporal lobe impairs the encoding of new memories and the retrieval of memories acquired immediately before the damage in human. In this study, we demonstrated that artificial visuoauditory memory traces can be established in the rat auditory cortex and that their encoding and retrieval depend on the entorhinal cortex of the medial temporal lobe in the rat. We trained rats to associate a visual stimulus with electrical stimulation of the auditory cortex using a classical conditioning protocol. After conditioning, we examined the associative memory traces electrophysiologically (i.e., visual stimulus-evoked responses of auditory cortical neurons) and behaviorally (i.e., visual stimulus-induced freezing and visual stimulus-guided reward retrieval). The establishment of a visuoauditory memory trace in the auditory cortex, which was detectable by electrophysiological recordings, was achieved over 20-30 conditioning trials and was blocked by unilateral, temporary inactivation of the entorhinal cortex. Retrieval of a previously established visuoauditory memory was also affected by unilateral entorhinal cortex inactivation. These findings suggest that the entorhinal cortex is necessary for the encoding and involved in the retrieval of artificial visuoauditory memory in the auditory cortex, at least during the early stages of memory consolidation.
Journal of Neuroscience 06/2013; 33(24):9963-74. · 6.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Human neural stem cells hold great promise for research and therapy in neural disease. We describe the generation of integration-free and expandable human neural progenitor cells (NPCs). We combined an episomal system to deliver reprogramming factors with a chemically defined culture medium to reprogram epithelial-like cells from human urine into NPCs (hUiNPCs). These transgene-free hUiNPCs can self-renew and can differentiate into multiple functional neuronal subtypes and glial cells in vitro. Although functional in vivo analysis is still needed, we report that the cells survive and differentiate upon transplant into newborn rat brain.
[Show abstract][Hide abstract] ABSTRACT: This paper presents direct evidences of the establishment of associative memory traces in the rat auditory cortex and the participation of the entorhinal cortex in the establishment and retrieval of these memory traces. We produced an association between cortical electrical activation and a visual stimulus with classical conditioning. The memory traces were physiologically visualized from auditory neuronal responses to the visual stimulus after conditioning and behaviorally confirmed with a memory recall experiment. Formation of new associative memory in the auditory cortex with classical conditioning was bilaterally blocked when the entorhinal cortex was unilaterally temporarily inactivated, but returned if the entorhinal cortex was not inactivated. Retrieval of the established associative memory in the ipsilateral neocortex was affected by the inactivation of the unilateral entorhinal cortex, while that in the contralateral neocortex was not affected, thus suggesting a less dependence of the hippocampal system in the retrieval than in the formation of associative memory. Supported by Hong Kong Research Grant Council (PolyU 9/CRF/09).
The Journal of the Acoustical Society of America 04/2012; 131(4):3442. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The thalamic reticular nucleus (TRN) is thought to function in the attentional searchlight. We analyzed the detection of deviant acoustic stimuli by TRN neurons and the consequences of deviance detection on the TRN target, the medial geniculate body (MGB) of the rat. TRN neurons responded more strongly to pure-tone stimuli presented as deviant stimuli (low appearance probability) than those presented as standard stimuli (high probability) (deviance-detection index = 0.321). MGB neurons also showed deviance detection in this procedure, albeit to a smaller extent (deviance-detection index = 0.154). TRN neuron deviance detection either enhanced (14 neurons) or suppressed (27 neurons) MGB neuronal responses to a probe stimulus. Both effects were neutralized by inactivation of the auditory TRN. Deviance modulation effects were cross-modal. Deviance detection probably causes TRN neurons to transiently deactivate surrounding TRN neurons in response to a fresh stimulus, altering auditory thalamus responses and inducing attention shift.
[Show abstract][Hide abstract] ABSTRACT: Responses to repeated auditory stimuli were examined in 103 neurons in the auditory region of the thalamic reticular nucleus (TRN) and in 20 medial geniculate (MGB) neurons of anesthetized rats. A further six TRN neurons were recorded from awake rats. The TRN neurons showed strong responses to the first trial and weak responses to the subsequent trials of repeated auditory stimuli and electrical stimulation of the MGB and auditory cortex when the interstimulus interval (ISI) was short (<3 s). They responded to the second trial when the interstimulus interval was lengthened to >or=3 s. These responses contrasted to those of MGB neurons, which responded to repeated auditory stimuli of different ISIs. The TRN neurons showed a significant increase in the onset auditory response from 9.5 to 76.5 Hz when the ISI was increased from 200 ms to 10 s (P<0.001, ANOVA). The duration of the auditory-evoked oscillation was longer when the ISI was lengthened. The slow recovery of the TRN neurons after oscillation of burst firings to fast repetitive stimulus was a reflection of a different role than that of the thalamocortical relay neurons. Supposedly the TRN is involved in the process of attention such as attention shift; the slow recovery of TRN neurons probably limits the frequent change of the attention in a fast rhythm.
Journal of Neurophysiology 12/2008; 101(2):980-7. · 3.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Electrical stimulation of the auditory cortex (AC) causes both facilitatory and inhibitory effects on the medial geniculate body (MGB). The purpose of this study was to identify the corticofugal inhibitory pathway to the MGB. We assessed two potential circuits: 1) the cortico-colliculo-thalamic circuit and 2) cortico-reticulo-thalamic one. We compared intracellular responses of MGB neurons to electrical stimulation of the AC following bilateral ablation of the inferior colliculi (IC) or thalamic reticular nucleus (TRN) in anesthetized guinea pigs. Cortical stimulation with intact TRN could cause strong inhibitory effects on the MGB neurons. The corticofugal inhibition remained effective after bilateral IC ablation, but it was minimized after the TRN was lesioned with kainic acid. Synchronized TRN neuronal activity and MGB inhibitory postsynaptic potentials (IPSPs) were observed with multiple recordings. The results suggest that corticofugal inhibition traverses the corticoreticulothalamic pathway, indicating that the colliculi-geniculate inhibitory pathway is probably only for feedforward inhibition.
Journal of Neurophysiology 07/2008; 99(6):2938-45. · 3.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neuronal responses to auditory stimuli and electrical stimulation were examined in 104 neurones in the auditory sector of thalamic reticular nucleus (TRN) and nine medial geniculate (MGB) neurones from anaesthetized guinea pigs. TRN neurones showed rhythmic spontaneous activities. TRN neurones changed firing pattern over time, from tonic to burst in a time interval of several seconds to tens of seconds. One-third of the TRN neurones (25/76) responded to the acoustic stimulus in a slow oscillation mode, either producing a spike burst at one time and responded with nothing another time, or producing a spike burst at one time and a single spike at the other. Thirty-two of 40 neurones received a corticofugal modulation effect. Nineteen of 32 neurones responded directly to electrical stimulation of the cortex with an oscillation of the same rhythm (7-14 Hz) as its auditory-evoked oscillation. Six neurones changed their firing pattern from burst to tonic when the auditory cortex was activated. As the TRN applied inhibition to the MGB, the oscillatory nature of inhibition would affect the fidelity of MGB relays. Thus, it was unlikely that the MGB was in relay mode when the TRN was in a slow oscillation mode. These results hint at a possible mechanism for the modulation of states of vigilance through the corticofugal pathway via the TRN.
The Journal of Physiology 12/2007; 585(Pt 1):15-28. · 4.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we investigated the relationship between c-fos expression in the auditory thalamus and corticofugal activation. The contribution of neurotransmitters and related receptors, the involvement of thalamic reticular nucleus (TRN), and the role of neuronal firing patterns in this process were also examined. The principal nuclei of the medial geniculate body (MGB) showed c-fos expression when the auditory cortex (AC) was activated by direct injection of bicuculline methobromide. However, no expression was detectable with acoustic stimuli alone. This indicated that c-fos expression in the principal nuclei of the MGB was triggered by the corticofugal projection. c-fos expression could be elicited in the MGB by direct injection of glutamate. Direct administration of acetylcholine, alternatively, had no effect. Bicuculline methobromide injection in the AC also triggered synchronized oscillatory activities sequentially in the AC and MGB. Cortically induced c-fos expression in the MGB was not mediated by a pathway involving the TRN because it remained intact after a TRN lesion with kainic acid. The present results also conclude that c-fos expression is not simply associated with firing rate, but also with neuronal firing pattern. Burst firings that are synchronized with the cortical oscillations are proposed to lead to c-fos expression in the principal nuclei of the MGB.
Proceedings of the National Academy of Sciences 08/2007; 104(28):11802-7. · 9.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the corticofugal modulation of acoustic information ascending through the auditory pathway of the rat, immunohistochemical techniques were used to study the functional expression of Fos protein in neurons. With auditory stimulation at different frequencies, Fos expression in the medial geniculate body (MGB), inferior colliculus (IC), superior olivary complex, and cochlear nucleus was examined, and the extent of Fos expression on the two sides was compared. Strikingly, we found densely Fos-labeled neurons in all divisions of the MGB after both presentation of an auditory stimulus and administration of a gamma-aminobutyric acid type A (GABA(A)) antagonist (bicuculline methobromide; BIM) to the auditory cortex. The location of Fos-labeled neurons in the ventral division (MGv) after acoustic stimulation at different frequencies was in agreement with the known tonotopic organization. That no Fos-labeled neurons were found in the MGv with acoustic stimuli alone suggests that the transmission of ascending thalamocortical information is critically governed by corticofugal modulation. The dorsal (DCIC) and external cortices (ECIC) of the IC ipsilateral to the BIM-injected cortex showed a significantly higher number of Fos-labeled neurons than the contralateral IC. However, no difference in the number of Fos-labeled neurons was found between the central nucleus of the IC on either side, indicating that direct corticofugal modulation occurs only in the ECIC and DCIC. Further investigations are needed to assess the functional implications of the morphological differences observed between the descending corticofugal projections to the thalamus and the IC.
The Journal of Comparative Neurology 05/2007; 501(4):509-25. · 3.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The neuronal interconnections between thalamus and cortex modulate information transmission in the central auditory system. To facilitate the understanding of its modulation effects and mechanism, first, the recent progress on investigating the anatomical connections and the physiological properties of the medial geniculate body and auditory cortex is summarized. Second, the connectional pattern and functional organization in thalamocortical and corticothalamic network are described. Third, the strategic position and role of the thalamic reticular nucleus in the auditory system are demonstrated. Lastly, the functional implication of this integrated system and possible interactions between auditory thalamus and cortex are discussed. The thalamocortical and corticothalamic projections may work as a dynamic filter array in integrating sensory information and optimizing signal processing in the auditory system.
[Show abstract][Hide abstract] ABSTRACT: In the present study, we investigated the auditory response features of the medial geniculate neurones, using in vivo intracellular recordings in anaesthetized guinea pigs. Of the 76 neurones examined, 9 showed 'off' or 'on-off' responses to an acoustic stimulus and thus were defined as 'off' or 'on-off' neurones. Among the remaining 67 neurones, 42 showed an excitatory postsynaptic potential (EPSP) to acoustic stimuli and 25 showed either a pure inhibitory postsynaptic potential (IPSP, 7 neurones), or an IPSP preceded by an EPSP (EPSP-IPSP type, 18 neurones). The EPSP responses exhibited a mean latency of 15.7 +/- 6.1 ms, which was significantly shorter than that of the IPSP responses (21.3 +/- 8.6 ms, P < 0.01). The IPSP responses also showed a significantly greater duration than the EPSP responses (208.5 +/- 128.2 ms versus 122.4 +/- 84.8 ms, P < 0.05), while there were no significant differences between the amplitudes of IPSP and EPSP (8.3 +/- 3.2 mV versus 8.7 +/- 5.3 mV). Of the 11 neurones that showed EPSP responses to acoustic stimuli and were histologically labelled, 7 were located in the lemniscal medial geniculate body (MGB) and 4 in the non-lemniscal MGB. Another 6 labelled neurones that showed IPSP responses to acoustic stimuli were located in the non-lemniscal MGB. With a membrane potential of above -72 mV, the neurones showed greater EPSP or IPSP to an acoustic stimulus when their membrane potential was depolarized. However, upon hyperpolarization to below -74 mV, the neurones shifted to low-threshold calcium spikes (LTS)/LTS bursts. In response to auditory stimuli of different durations, 'off' neurones that responded to the offset of the acoustic stimulus and were located in the non-lemniscal MGB showed different response latencies or deviations of latencies in addition to exhibiting different numbers of spikes, suggesting that the timing of the spikes could be another component utilized by thalamic neurones to encode information on the stimulus. Given that some non-lemniscal neurones are multisensory and project to the entire auditory cortex, the selective corticofugal inhibition in the non-lemniscal MGB would enable the ascending pathway to prepare the auditory cortex to receive subsequent auditory information, avoiding the interference of other sensory inputs.
The Journal of Physiology 11/2004; 560(Pt 1):191-205. · 4.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the present study, we investigated neuronal responses to acoustic stimuli and cortical stimulation in the medial geniculate body (MGB) through in vivo intracellular recordings in anaesthetized guinea pigs. Of the 54 neurones examined with acoustic stimuli, 36 showed excitatory postsynaptic potential (EPSP) responses and 19 showed inhibitory postsynaptic potential (IPSP) responses to acoustic stimuli. Of the 36 EPSP neurones examined with corticofugal modulation, 29 received corticofugal depolarization, 3 corticofugal inhibition, and 4 showed no effect. Of the 19 IPSP neurones, 17 received corticofugal inhibition and 2 were not affected. The mean amplitude of the EPSPs evoked by acoustic stimuli was similar to that evoked by the electrical cortical stimulation (9.19 +/- 5.55 mV versus 9.22 +/- 5.16 mV). There was a significant correlation between the parameters of the EPSPs evoked by an acoustic stimulus and those evoked by cortical stimulation. The mean amplitude of the IPSP evoked by electrical cortical stimulation was significantly greater than that evoked by acoustic stimuli (11.6 +/- 3.8 mV versus 9.1 +/- 3.7 ms, P < 0.05). Seven auditory EPSP and 7 IPSP neurones were examined with corticofugal modulation and labelled with Neurobiotin. Of the 7 EPSP neurones, 5 showed excitatory responses to cortical stimulation and 2 demonstrated no effects. Four of the 5 neurones that received corticofugal depolarization were located in the lemniscal MGB and 1 in the non-lemniscal MGB; of the remaining 2, 1 was located in the lemniscal and the other in the non-lemniscal MGB. Of the 7 IPSP neurones, 1 received an excitatory corticofugal input followed by an inhibitory input and 4 received only an inhibitory corticofugal input, while the remainder demonstrated no corticofugal effects. All 7 neurones were located in the non-lemniscal MGB. The result that both ascending and descending inputs caused similarly shaped EPSPs reflects a neuronal endogenous characteristic irrespective of the physical locations of the synapses. The IPSP responses to both acoustic stimuli and electrical cortical stimulation are likely to be caused by feedback from the thalamic reticular nucleus.
The Journal of Physiology 11/2004; 560(Pt 1):207-17. · 4.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to test the structural stability and reliability of the Swedish occupational fatigue inventory (SOFI) for use in a group of Chinese visual display terminal (VDT) workers. A qualified translator was recruited to translate the Chinese version of the SOFI (SOFI-C). The content validity was established with 12 bilingual practitioners and seven professional experts. The translated SOFI was administered to 104 sedentary workers on two occasions with an interval of 60 min. Most of them were female (80.8%) and they had a mean age of 34.5 years. Fifty-one percent of them reported using a VDT for 4h or more at work. Exploratory factor analysis revealed a five-factor solution, which was comparable to the original latent factors. Cronbach's alpha for the five-factor scales was between 0.88 and 0.95. The test-retest reliability was satisfactory with intra-class correlations ranging from 0.69 to 0.83. The workers who used a VDT for 4h or more had significantly higher SOFI scores than those who used one for less than 4 h (p = 0.007 - 0.046). The results indicated that the SOFI-C was valid and reliable for measuring fatigue among Chinese sedentary workers. The satisfactory structural stability suggested that cultural influences on the construct of fatigue were not strong. Its characteristics of discrimination of the sedentary workers who had high VDT exposure suggested that the SOFI-C would be a useful instrument for prevention and intervention programs designed for work-related injuries in the workplace.