Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice / 神经科学通报·英文版

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.

Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice / 神经科学通报·英文版

While the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.

The establishment of positive and negative evaluative conditioning reflex of neutral facial expression / 中华行为医学与脑科学杂志

Objective To examine the effect of positive and negative evaluative conditioning (EC) on neutral faces.Methods The experiment consisted of three phases:baseline phase,conditioning phase,and re-evaluative phase,in which 41 college students participated,watching sequences of neutral faces (CS) pairing to either a positive stimulus (USpos) or a negative stimulus (USneg).Their emotional experiences (valence and arousal) and physiological reactivity (eyeblink startle reflex and skin conductance) were recor ded.Results (1) In the re-evaluative phase,CSpos was rated significantly more positive than CSneg and CSneut,while CSneg was rated significantly more negative than CSneut (CSpos (5.05± 1.24),CSneg (3.73± 1.48),CSneut (4.46± 1.04),P＜0.05).(2)In the re-evaluative phase,the mean startle eyeblink response magnitude(T score) to CSpos was significantly smaller than the responses elicited by CSneg and CSneut (CSpos (45.04±5.56),CSneg (51.44±9.30),CSneut (54.52± 10.60),P＜0.01).Conclusion The findings suggest that neutral faces can acquire valences and approach motivation through EC.

Establishment of delay eyeblink conditioned reflex and the acquisition rule in cynomolgus monkey / 中华行为医学与脑科学杂志

Objective To investigate the method of establishing a model of delay eyeblink condi-tioning ( DEC) in no surgical cynomolgus monkey and analyze the related acquisition rule.Methods Using the special monkey chairs to fix 6 adult male cynomolgus monkeys,they were sitting on the chairs and keep-ing awake,and heads could rotate freely during the whole training session.In the experiment,the 6 monkeys were trained in DEC with a tone (500 ms,85 dB) as the conditioned stimulus (CS),paired with a corneal oxygen-puff (100 ms,5 psi) as the unconditioned stimulus (US).There were 120 trials per-session,and 2 sessions per-day.During the experiments,an infrared emitter/detector attached to spectacles for eyeblink re-cording,the data of conditioned response ( CR) and startle response ( SR) were analyzed offline.Result-s Among the 6 cynomolgus monkeys,4 of them completed all of the training process of DEC and 3 monkeys had successful acquisition of DEC.The average CR rate in the last training session reached ( 64.67 ± 2.00)%,(P<0.01);1 monkey only showed a high acquisition rate( 85.00%) at the first training session, and the low CR rate in the next training sessions with the average rate of 18.16%,suggesting that the DEC model was failed to established.The SR rates in 4 cynomolgus monkeys were low with average rate of 5.47%. Conclusion Although the DEC behavior training of the cynomolgus monkey is easy to be influenced by many inside or outside factors,DEC can be obtained under the condition of non surgery and proper braking.

Reinstatement of short-latency responses after asymptotic Pavlovian conditioning training by the presentation of an extraneous stimulus

The purpose of this study was to examine whether the progressive disappearance of short-latency conditioned responses, or inhibition of delay, observed in Pavlovian conditioning with long inter-stimulus intervals, could be reverted by the presentation of a novel stimulus. In one experiment, two groups of rabbits received extensive training with a short (250 ms) or a long (1500 ms) tone that overlapped and terminated with a periorbital shock unconditioned stimulus. After training, the presentation of an extraneous stimulus prior to tone onset produced a reinstatement of short latency CRs in the group trained with the long CS, but did not affect CR latency in the group trained with the short CS. This finding is consistent with Pavlov's (1927) view that conditioning with long conditioned stimuli involves the acquisition of response tendencies in the early portion of the stimulus that are subsequently suppressed by the development of an inhibitory process.

Establishment of delay-trace conditioning procedure of classical eyeblink conditioning in Kunming mice and analysis of behavioral characteristic parameters / 中华行为医学与脑科学杂志

ObjectiveTo investigate the characteristic parameters and variation of acoustic startle reflex (ASR) and conditioning response (CR)during the acquisition of delay-trace eyeblink conditioning.Methods15healthy Kunming mice were randomly divided into 3 groups:single-task DEBC group ( n =5 ) ; single-task TEBC group ( n =5) ; dual delay/trace group ( n =5).Three groups received paired training of tone conditioned stimulus(CS)in different audio frequency (TEBC groups:2KHz; DEBC group:1KHz) and a 100 ms comeal oxygenpuff unconditioned stimulus(US).Then observed the characteristic parameters of ASR and CR.ResultsAfter pairing training for 10 days,ASR rate( ASR％ ) of single-task groups ( 10th day (38.00 ± 8.64) ％ and (38.55 ±12.41 ) ％ respectively,time effect:F =4.574,P =0.008 ; group effect:F =2.021,P =0.193 ) and dual delaytrace group ( 10th day (47.95 ± 14.23 ) ％ and (62.01 ± 9.03 ) ％ respectively,time effect:F =5,547 P =0.013 ;group effect:F =0.738,P =0.415) changed significantly with the following training but between single-task groups or dual delay-trace group.CR rate ( CR％ ) of single-task groups ( 10th day were (45.4 ± 5.39) ％ and (65.6 ± 6.77) ％ respectively,time effect:F =9.558,P =0.000 ; group effect:F =5.117,P =0.054 ) and dual delay/trace group ( 10th day (57.66 ± 4.34) ％ and (77.35 ± 7.36) ％ respectively,time effect:F =7.750,P =0.002 ;group effect:F=1.449,P=0.263 ) showed obvious change with the following training but between singletask groups or dual delay-trace group.Peak amplitude of single-task DEBC group ( time effect F =2.679,P =0.017 ) and dual delay-trace group ( F=3.452,P=0.034 ) had increased significantly with the following training.Peak latency showed no obvious change.ConclusionDual delay-trace conditioning procedure of classical eyeblink conditioning and single-task can be successfully established in Kunming mice.Although there are some variations,those can be controled and be weaken effect of them by taking targeted measures.

Potential Significance of Eyeblinks as a Behavior Marker of Neuropsychiatric Disorders

The primary purpose of this review is to present an overview of relationship between human spontaneous eyeblinking and internal cognitive processes. The second purpose is to address the neural substrates of human eyeblinking based on recent studies focusing on the central dopaminergic system and to explore the significance of spontaneous eyeblinks in neuropsychiatric disorders. We reviewed recent and previous studies on eyeblink patterns under various cognitive tasks. We also reviewed neural substrates of eyeblinking, particularly based on the central dopaminergic system. This paper suggests that spontaneous eyeblinks are highly correlated with various cognitive processes and the activity of central dopaminergic system. Various neuropsychiatric disorders are related to the alteration of the occurrence of eyeblinking. Spontaneous eyeblinking is the unique human behavior that occurs regularly without conscious effort. It is known that the rate of eyeblinking is modulated by internal cognitive processes and dopamine-related neuropsychiatric disorders. Further research is required to how the temporal dynamics of spontaneous eyeblinking is correlated with the disease activity and progression.

Effects of 860 MHz electromagnetic radiation on dual task eyeblink conditioning in guinea pigs / 中华物理医学与康复杂志

Objective To observe the effects of 860 MHz microwave radiation on an established dual task model of trace and delay eyeblink conditioning in guinea pigs.Methods Twenty-four guinea pigs with an established dual task model of trace and delay eyeblink conditioning were assigned randomly into four groups : a microwave-exposed 1 h group, a microwave-exposed 20 min group, a sham-exposed group and a normal control group.The guinea pigs in the 1 h and 20 min groups were irradiated on the head daily for 3 days using 860 MHz electromagnetic radiation at a power density of 1 mW/cm2 for 1 h and for 20 min, respectively. After radiation the guinea pigs were trained with classical dual task eyeblink conditioning.Results Compared with the normal control group, the behavioral parameters (acquisition rate and peak amplitude of trace and delay eyeblink) of guinea pigs in the microwave-exposed 1 h group had decreased significantly with no obvious change in latency. The behavioral parameters of guinea pigs in the microwave-exposed 20 min group, the sham-exposed group and the normal control group showed no obvious change.Conclusions Microwave radiation at 860 MHz and 1.0 mW/cm2 for 1 h can cause changes in dual trace and delay eyeblink conditioning in guinea pigs and decrease learning and memory capacity.

Condicionamiento clásico y cognición implícita / Classical conditioning and implicit cognition

En su conjunto, las evidencias experimentales conductuales y psicobiológicas revisadas en este artículo muestran que el condicionamiento clásico humano tiene una justificación evolutiva, se desarrolla mediante un procesamiento cognitivo diferente del procesamiento consciente y se sustenta en estructuras cerebrales diferentes. Dichas estructuras no suelen funcionar desligadas y por ello la combinación de ambas formas de procesamiento, explícito e implícito, es el patrón general en condiciones naturales. De hecho, debido a la organización jerárquica del sistema nervioso, suele existir un proceso de control de arriba hacia abajo (cortical-subcortical) pero, bajo condiciones especiales de laboratorio, puede hacerse evidente en la conducta, por ejemplo mediante los paradigmas de miedo condicionado, la estrecha relación entre procesamiento implícito y el condicionamiento clásico en nuestra especie.

Experimental data, behavioral and psychobiological, reviewed in this paper show that human classical conditioning has an evolutionary purpose, it is developed by means of a cognitive processing different from the conscious processing, and sustained by different cerebral structures. These structures usually do not work isolated. For that reason, combination of both forms of processing, explicit/implicit, is the general pattern in natural conditions. In fact, due to the hierarchical organization of the nervous system, usually it exists a top-down control process (cortical-subcortical) but, under special conditions of laboratory, can be behaviorally evident, for example by means of the fear conditioning, close relationship between implicit processing and Pavlovian conditioning in humans.

Activity of Single Granule Cell in the Dentate Gyrus of Guinea Pig During The Consolidation of Trace Eyeblink Conditioned Responses / 生物化学与生物物理进展

The hippocampus plays a critical role during the consolidation of trace eyeblink conditioned responses (CRs). However, the role of its related structure such as dentate gyms (DG) remains unclear. The present study was aimed at monitoring the activity of single granule cell in the DG during the consolidation of trace eyeblink CRs, and elucidating the possible role of DG during this hippocampus-dependent task. Guinea pigs (n=8) were trained on a trace eyeblink conditioning paradigm using a 200-ms tone conditioned stimulus (CS), a 200-ms corneal airpuff unconditioned stimulus (US) and a 600-ms trace interval. Controls consisted of pseudo- conditioned guinea pigs (n=8). Extracellular single unit recordings in vivo were performed in the DG of learner animals during the consolidation of trace eyeblink CRs. The results revealed that all the trace-conditioned animals acquired the trace eyeblink CRs over 14 training days, however, none of the pseudo-conditioned animals did. Furthermore, 23 of 40 single granule cells in the DG of learner animals exhibited heterogeneous activity patterns during the consolidation of trace eyeblink CRs such as increases in activities to the tone CS, trace interval or airpuff US. The results suggested that the DG might participate in the neural circuit important for the consolidation of trace eyeblink CRs, and that the granule cells might encode different information during the consolidation of trace eyeblink CRs.

Microinjection of Muscimol into cerebellular dentate-interpositus nuclei affects acquisition of classical eyeblink conditioning in guinea pigs / 第三军医大学学报

Objective To investigate the role of cerebellar dentate-interpositus (D-I) nuclei during acquisition of classical eyeblink conditioning in guinea pigs. Methods A 500 ms tone conditioned stimulus (CS) was paired with a 100 ms corneal oxygen-puff unconditioned stimulus (US) in a delay paradigm. Guinea pigs were trained daily to acquire the classically conditioned eyeblink responses. Micorinjections of Muscimol into bilateral cerebellar D-I nuclei were performed during the 4-6 day of training session. A high-resolution potentiometer was used to detect the eyeblink responses. Results The conditioned response (CR) rates of Muscimol-injected group on session 4-6 were significantly lower than their rates on session 3 (P1=0.005,P2=0.004,P3=0.010); Their rates on session 7 and 8 were as the same level as those without microinjection on session 4 and 5 (P1=0.061,P2=0.669). However, there was no significant difference on their amplitude and peak latency of unconditioned responses (URs) during the entire course of training (P1=0.926,P2=0.939). Conclusion The cerebellar D-I nucleus is actively involved in the neural circuitry of motor learning, which is essential for both acquisition and performance of the classically conditioned eyeblink responses.