Bo Hu

Third Military Medical University, Ch’ung-ch’ing-shih, Chongqing Shi, China

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Publications (13)38.81 Total impact

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    ABSTRACT: Stimulus-evoked theta oscillations are observed in the medial prefrontal cortex (mPFC) when executing a variety of learning tasks. Here, we aimed to further determine whether spontaneous theta-band (5.0-10.0Hz) oscillations in the mPFC predicted the subsequent behavioral performance in trace eyeblink conditioning (TEBC), in which the conditioned stimulus (CS) was separated from the unconditioned stimulus (US) by 500-ms trace interval. By recording local field potentials (LFP) signals in the guinea pigs performing the TEBC task, we found that, a higher mPFC relative theta ratio [theta/(delta+beta)] during the baseline (850-ms period prior to the onset of the CS) was predictive of higher magnitude and more adaptive timing rather than faster acquisition of trace conditioned eyeblink responses (CR). However, the prediction of baseline mPFC theta activity was time-limited to the well-learning stage. Additionally, the relative power of mPFC theta activity did not correlate with the CR performance if the trace interval between the CS and the US was shortened to 100ms. These results suggest that the brain state in which the baseline mPFC theta activity is present or absent is detrimental for the subsequent performance of trace CRs especially when the asymptotic learning state is achieved.
    Behavioural brain research 02/2014; · 3.22 Impact Factor
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    ABSTRACT: Research concerning impairment of associative learning during aging remains limited. The senescence-accelerated mice (SAM) prone/8 (P8) has been proposed as a useful model for the study of aging, and SAM resistant/1(SAMR1) is its control as a normal aging strain. Classical eyeblink conditioning has long been served as a model of associative learning. In order to explore the effects of aging on associative learning in SAM, the present study successively tested three paradigms of eyeblink conditioning in SAMP8 and SAMR1: classical single cue trace eyeblink conditioning (TEC), discriminative trace eyeblink conditioning and reversal learning of TEC. Behavioral performance indicated that SAMP8 could acquire limited single-cue trace eyeblink conditioning task and two-tone discrimination trace eyeblink conditioning with a relative lower acquisition rate compared to SAMR1. Both SAMP8 and SAMR1 failed to acquire reversal learning of discriminative TEC, and SAMP8' startle reflex to tone CS was lower than SAMR1. These results indicated that the impairments of aging on associative learning were incomplete in SAMP8.
    Behavioural brain research 09/2013; · 3.22 Impact Factor
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    ABSTRACT: In a process known as frequency-specific plasticity, electrical stimulation of the ventral division of the medial geniculate body (MGBv) in the thalamus evokes a shift in the frequency-tuning curves of auditory cortical (AC) neurons towards the best frequency (BF) of stimulated MGBv neurons. However, the underlying synaptic mechanisms of this process are uncharacterized. To investigate whether this dynamic change depends on thalamocortical (TC) synaptic plasticity, we studied frequency-specific changes in synaptic transmission efficacy in TC pathways evoked by thalamic stimulation. Specifically, we induced cortical plasticity by repetitive focal electrical stimulation of the MGBv in rats and measured receptive field shifts and local field potentials in AC neurons. Our data show that focal electrical stimulation of the MGBv induced receptive field shifts as well as long-term potentiation or depression of the local field potentials in AC neurons. The evoked potentiation and depression depended on the frequency of the electrical stimulation of the MGBv synchronized with the BF of MGBv and AC neurons. Receptive field shifts were produced by inhibition of responses at the BF of the recorded AC neurons and facilitation of responses at the BF of the stimulated MGBv neurons. These results suggest that MGBv neurons play a decisive role in the expression of AC synaptic plasticity and that activation of different frequency-specific TC pathways may be the synaptic mechanism underlying this plasticity.
    Neuroscience Letters 09/2013; · 2.03 Impact Factor
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    ABSTRACT: Behavioral studies have demonstrated that both medial prefrontal cortex (mPFC) and cerebellum play critical roles in trace eyeblink conditioning. However, little is known regarding the mechanism by which the two brain regions interact. By use of electrical stimulation of the caudal mPFC as a conditioned stimulus, we show evidence that persistent outputs from the mPFC to cerebellum are necessary and sufficient for the acquisition and expression of a trace conditioned response (CR)-like response. Specifically, the persistent outputs of caudal mPFC are relayed to the cerebellum via the rostral part of lateral pontine nuclei. Moreover, interfering with persistent activity by blockade of the muscarinic Ach receptor in the caudal mPFC impairs the expression of learned trace CRs. These results suggest an important way for the caudal mPFC to interact with the cerebellum during associative motor learning.
    The Cerebellum 09/2013; · 2.60 Impact Factor
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    ABSTRACT: The cerebellum plays an essential role in motor learning. Recently, orexins, the newfound lateral hypothalamic neuropeptides, have been found to excite Purkinje cells in the cerebellar cortex and neurons in the deep cerebellar nuclei (DCN). However, little is known about their roles in cerebellum-dependent motor learning. Therefore, the present study was designed to investigate the functional significance of hypothalamic orexinergic system during trace eyeblink conditioning, a tractable behavioral model system of cerebellum-dependent motor learning. It was revealed that the orexin 1 receptors (OXR1) were specifically localized on the soma of Purkinje cells and large DCN neurons. Furthermore, interfering with the endogenous orexins' effects on the cerebellum via the selective OXR1 antagonist SB-334867 disrupted the timing rather than the acquisition of trace conditioned eyeblink responses. In addition to the behavioral effects, the SB-334867 prevented the increase in peak amplitude of cerebellar theta oscillations with learning. These results suggest that the endogenous orexins may modulate motor learning via the activation of cerebellar OXR1.
    Behavioural brain research 05/2013; · 3.22 Impact Factor
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    ABSTRACT: The role of the hippocampus in delay eyeblink conditioning (DEC) remains controversial. Here, we investigated the involvement of the hippocampus in DEC with a soft tone as the conditioned stimulus (CS) by using electrolytic lesions or muscimol inactivation of guinea pig dorsal hippocampus. Interestingly, when a soft tone was used as a CS, electrolytic lesions of the hippocampus significantly retarded acquisition of the conditioned response (CR), and muscimol infusions into hippocampus distinctly inhibited the acquisition and expression of CR, but had no significant effect on consolidation of well-learned CR. In contrast, both electrolytic lesions and muscimol inactivation of hippocampus produced no significant deficits in the CR when a loud tone was used as the CS. These results demonstrate that the hippocampus is essential for the DEC when the delay task was rendered more difficult.
    PLoS ONE 01/2013; 8(8):e71249. · 3.73 Impact Factor
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    ABSTRACT: Disruption of ionic homeostasis and neuronal hyperexcitability contribute to early brain injury after subarachnoid hemorrhage (SAH). The hyperpolarization-activated/cyclic nucleotide (HCN)-gated channels play critical role in the regulation of neuronal excitability in hippocampus CA1 region and neocortex, in which the abnormal neuronal activities are more readily provoked. This study was to investigate the interactions between HCN channels and hyperneuronal activity after experimental SAH. The present results from whole-cell recordings in rat brain slices indicated that (1) perfusion of hemoglobin (Hb)-containing artificial CSF produced neuronal hyperexcitability and inhibited HCN currents in CA1 pyramidal neurons, (2) nitric oxide/Spermine (NO/Sp), a controlled releaser of nitric oxide, attenuated neuronal excitability and enhanced HCN currents in CA1 pyramidal neurons, while L-nitroarginine (L-NNA), an inhibitor of nitric oxide synthase, reduced the HCN currents; and (3) the inhibitory action of Hb on HCN currents was reversed by application of NO/Sp, which also reduced neuronal hyperexcitability; conversely, L-NNA enhanced inhibitory action of Hb on HCN currents. Additionally, Hb perfusion scavenged the production of nitric oxide and decreased the expression of HCN1 subunits in CA1 region. In the rat SAH model, the expression of HCN1, both at mRNA and protein level, decreased in hippocampus CA1 region at 24 h and more pronounced at 72 h after SAH. These observations demonstrated a reduction of HCN channels expression after SAH and Hb reduced HCN currents in hippocampus CA1 pyramidal neurons. Inhibition of HCN channels by Hb may be a novel pathway for inducing the hyperneuronal excitability after SAH.
    Journal of Neuroscience 02/2012; 32(9):3164-75. · 6.91 Impact Factor
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    ABSTRACT: Learning-induced changes of synaptic ultrastructure have long been proposed as a mechanism that may contribute to support memory formation. Although recent studies have demonstrated that the interpositus nuclei (IN) play critical role in acquisition and retention of trace conditioned eyeblink responses (CRs), there is now limited evidence associating trace eyeblink conditioning with changes of synaptic ultrastructure in the IN. Here, we investigated this issue using a transmission electron microscope. Adult guinea pigs were randomly allocated to either a trace-paired, delay-paired, unpaired or exposure-only condition. The IN tissue was taken for morphological analysis 1h after the completion of the tenth training session. Serial section analysis of synaptic ultrastructure revealed that trace eyeblink conditioning induced increases in the thickness of excitatory PSD. Classification of the synapses into shape subtypes indicated that the increased thickness of excitatory PSD was mainly attributable to increase in the concave- and convex-shaped synapses. On the contrary, trace eyeblink conditioning resulted in decreases in the thickness of inhibitory PSD. Specifically, these significant changes of PSD thickness were limited to occur in the animals with good behavioral performance. Further analysis of correlations between the trace CR performance and synaptic ultrastructural modifications showed that the thickness of excitatory PSD within the IN correlated with the peak amplitude of trace CRs, whereas the thickness of inhibitory PSD correlated with the onset latency. The present findings suggest that trace eyeblink conditioning induces structural plasticity in the IN, which may play a crucial role in acquiring and executing adaptive eyeblink movements.
    Behavioural brain research 01/2012; 226(2):529-37. · 3.22 Impact Factor
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    ABSTRACT: Short-term sleep deprivation (SD) has been shown to enhance cortical activity. However, alterations in the cellular excitability of cortical neurons following SD are not yet fully understood. The present study investigated the effects of 4-hour SD on pyramidal neurons in the prefrontal cortex (PFC) of rats using whole-cell patch-clamp recording. SD led to an increase in the initial slope of firing frequency-current curve and a decrease in frequency adaptation, which were reversed by recovery sleep (RS). Correspondingly, the total afterhyperpolarization (AHP) was reduced in the SD group and returned in the RS group. Furthermore, the component of AHP changed after SD seemed to be sensitive to Ca(2+). These observations indicate an enhancement in intrinsic excitability due to short-term SD, and suggest a role for Ca(2+)-dependent AHP in this change. The findings of the present study may provide a possible explanation for the SD-induced increase in cortical activity.
    Brain research 07/2011; 1401:52-8. · 2.46 Impact Factor
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    ABSTRACT: Trace conditioning of the eyeblink reflex, a form of associative motor learning in which presentations of the conditioned stimulus (CS) and the unconditioned stimulus (US) are separated in time by a silent trace interval, requires intact forebrain structures such as the hippocampus and medial prefrontal cortex. Recently, increased learning-related activities have also been observed in specific cerebellar cortical area such as the lobule of HVI during this conditioning task. To date, however, it remains controversial how the cerebellar cortex contributes to trace eyeblink conditioning. In the present study, we addressed this issue by reversibly suppressing the cerebellar cortical inhibition via microinjections of the GABA(A) receptor antagonist bicuculline methiodide (BICM) into the interpositus nucleus of guinea pigs. We showed that, in the well-trained guinea pigs, the BICM administrations failed to abolish the acquired trace-conditioned eyeblink responses (CRs). Although the acquired trace CRs were mostly retained, their peak latencies were shortened and their peak amplitudes diminished as evidenced by only half of the spared trace CRs preserving the topography of adaptive peak latencies or middle-/high-peak amplitudes. In the same animals, the acquired trace CRs were abolished by microinjections of the GABA(A) receptor agonist muscimol and were unaffected by microinjections of the artificial cerebrospinal fluid. Furthermore, we demonstrated that with concurrent BICM-induced suppression of the cerebellar cortical inhibition and presentations of the tone CSs in the guinea pigs receiving unpaired conditioning training, CR-like eyeblink responses were not generated. Altogether, these results support the hypothesis that GABAergic neurotransmission from cerebellar cortex to the interpositus nucleus may participate in regulating the expression of acquired trace CRs.
    Brain research 04/2010; 1337:41-55. · 2.46 Impact Factor
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    ABSTRACT: The cerebellum has been proved to be essential for the acquisition of delay eyeblink conditioning, but its contribution to the acquisition of trace eyeblink conditioning (TEBC) has not been fully determined. In the present study, using chemically reversible inactivation techniques, we examined the relative contribution of ipsilateral cerebellum to the acquisition of TEBC using different time length of trace interval (TI) in guinea pigs. It was found that inactivations of the left intermediate cerebellum with a GABA(A) receptor agonist muscimol during training completely prevented the acquisition of TEBC using a relatively short (50 ms) TI, instead of the acquisition of TEBC using a relatively long (250 ms) TI. However, inactivations of the left intermediate cerebellum totally abolished the well-established left trace conditioned eyeblink responses (CRs) regardless of the time length of TI. These results suggested that while the ipsilateral cerebellum is essential for the expression of trace CRs, its contribution to the acquisition of trace CRs appears to mainly depend on the time length of TI.
    Neuroscience Letters 06/2009; 459(1):41-5. · 2.03 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the relative contributions of the ipsilateral and contralateral cerebellum to the acquisition of unilateral classical eyeblink conditioning (EBCC). The unilateral EBCC was achieved using a binaural tone conditioned stimulus (CS) paired with a left airpuff unconditioned stimulus (US). A high-resolution potentiometer was used to monitor eyeblink responses. Guinea pigs received one CS-US session followed by three CS-US sessions (sessions 2 to 4), during which microinjections of muscimol, a GABA(A) receptor agonist, were performed to reversibly inactivate the cerebellum unilaterally prior to training. To test whether any learning had occurred during these inactivation sessions, training was continued for six more CS-US sessions (sessions 5 to 10) without any inactivation. Animals with inactivation of the left cerebellum had no signs of left conditioned response (CR) during sessions 2 to 4, and their CR acquisition during sessions 5 to 10 was not distinguishable from that of control animals during sessions 2 to 7. In contrast, animals with inactivation of the right cerebellum acquired left CRs during sessions 2 to 4, although their CR acquisition was significantly retarded during session 2. In addition, microinjections of muscimol into the right cerebellum did not affect left neuro-behavioral activity. Finally, microinjections of muscimol into either the left or the right cerebellum did not affect the performance of tone-airpuff evoked unconditioned response (UR). In contrast to the essential role of the ipsilateral cerebellum, the contralateral cerebellum is potentially involved in the acquisition of unilateral EBCC during the early stage of training.
    Acta Pharmacologica Sinica 02/2009; 30(2):141-52. · 2.35 Impact Factor
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    ABSTRACT: Objective To explore the possible mechanisms that cause the dentate gyrus (DG) neurons to play different roles in information coding. Methods In vivo extracellular single unit recording was performed on 22 waking female guinea pigs, which were positioned in a sound-attenuated recording chamber without any muscular relaxants. The spontaneous firing patterns of the DG neurons were detected and compared. Results There were two different electrophysiological populations in the DG of guinea pigs, principal cells (PCs) and fast spiking interneurons (INs). Of the PCs, 1.3% discharged regularly, 48.1% irregularly and 50.6% in bursts; in contrast, of the INs units, 64.1% discharged regularly, 2.6% irregularly and 33.3 % in bursts. The spontaneous firing patterns of PCs were significantly different from those of INs (P <0.01). In addition, the differences of several interspike interval (ISI) parameters also have been observed: (1) the ISI coefficients of variation of PCs (3.39 +/- 3.56) were significantly higher than those of INs (1.08 +/- 0.46) (P < 0.01 ); (2) the ISI asymmetric indexes of PCs (0. 047 +/- 0. 059) were significantly lower than those of INs (0. 569 +/-0. 238) (P < 0.01). Conclusion In the DG, the spontaneous firing patterns of PCs were significantly different from those of INs. The former were prone to fire in bursts, the latter were prone to fire regularly. The different roles in information coding between PCs and INs might be caused by their different firing patterns.
    Neuroscience Bulletin 01/2006; 22(1):21-8. · 1.37 Impact Factor

Publication Stats

41 Citations
38.81 Total Impact Points


  • 2006–2014
    • Third Military Medical University
      • • Department of Physiology
      • • Department of Neurosurgery
      Ch’ung-ch’ing-shih, Chongqing Shi, China