Characterizing the functional significance of the neonatal rat vibrissae prior to the onset of whisking

The present series of experiments assessed how information from the whiskers controls and modulates infant rat behavior during early learning and attachment. Passive vibrissal stimulation can elicit behavioral activity in pups throughout the first two postnatal weeks, although orienting to the source of stimulation is evident only after ontogenetic emergence of whisking. In addition, while pups were capable of demonstrating learning in a classical conditioning paradigm pairing vibrissa stimulation with electric shock, no corresponding changes were detected in the anatomy of the barrel cortex as determined by cytochrome oxidase (CO) staining. Finally, the role of whiskers in a more naturalistic setting was determined in postnatal day (PN)3-5 and PN11-12 pups. Our results showed that both nipple attachment and huddling were disrupted in whisker-clipped PN3-5 pups but only marginally altered in PN1I 1-12 pups. Together, these results suggest that the neonatal whisker system is behaviorally functional and relevant for normal mother-infant interactions, though it lacks the sophistication of a mature whisker system that evokes very specific and directed responses.     

Maternal zinc deficiency reduces NMDA receptor expression in neonatal rat brain, which persists into early adulthood

Prenatal and early postnatal zinc deficiency impairs learning and memory and these deficits persist into adulthood. A key modulator in this process may be the NMDA receptor; however, effects of zinc deficiency on the regulation of NMDA receptor activity are not well understood. Female Sprague-Dawley rats were fed diets containing 7 (zinc deficient, ZD), 10 (marginally zinc deficient, MZD) or 25 (control) mg Zn/g diet preconception through postnatal day (PN) 20, at which time pups were weaned onto their maternal or control diet. Regulation of NMDA receptor expression was examined at PN2, PN11, and PN65. At PN2, expression of whole brain NMDA receptor subunits NR1, NR2A, and NR2B was lower in pups from dams fed ZD and MZD compared to controls, as analyzed using relative RT-PCR and immunoblotting. At PN11, whole brain and hippocampi NR1, NR2A, NR2B and PSA-NCAM (polysialic acid-neural cell adhesion molecule) expression and the number of PSA-NCAM immunoreactive cells were lower in pups from dams fed ZD compared to controls. Whole brain brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) concentrations were lower in pups from dams fed ZD or both low zinc diets, respectively. Whole brain NR1 expression remained lower in previously zinc-deficient rats at PN65. These data indicate potential mechanisms through which developmental zinc deficiency can impair learning and memory later in life.     

去胡须对大鼠行为及桶状皮层的影响

目的:研究外周去胡须后大鼠行为及桶状皮层(barrel cortex,BC)的可塑性变化。方法:SD大鼠随机分组(n=4):正常对照(A组),出生后第2天去除双侧颊脂垫组(B组),出生后第2天去除右侧颊脂垫组(C组),出生后1～5d每天剪右侧胡须,从出生后第5天起不剪由其胡须自由生长组(D组)。出生后第30天时称体重,测量左侧D2胡须长度,观测行为学变化(如狭缝实验、自由探索行为和趋壁行为)。采用细胞色素氧化酶组织化学法研究barrel排列与发育情况。结果:A组能迅速辨别出正确狭缝并钻入,平均用时(5.6±2.3)s;B组大鼠只有当鼻尖碰到狭缝壁时才会钻入狭缝。C组大鼠当其右侧脸颊靠近狭缝时,不能辨别出狭缝,只有当其掉转身体,用左侧胡须探测时才可能迅速钻入正确的狭缝。D组的表现同C组,B、C、D组大鼠进入正确狭缝的所用时间均显著长于A组(P0.01,P0.05,P0.01)。去除双侧颊脂垫的大鼠其左趋壁时间、右趋壁时间以及总趋壁时间均较正常大鼠短。去除右侧颊脂垫组的大鼠右趋壁时间也显著短于正常(P0.05)。四组大鼠左侧D2胡须长度以及体重均无显著差异。从出生后第2天时一直剪除右侧胡须的小鼠在出生后第30天时发现其barrel变小,排列较混乱,barrel之间的界限不清,皮层细胞色素氧化酶(CO)反应的灰度明显变淡。结论:外周去传入不引起大鼠体重改变及残留胡须长度的代偿性改变,但可引起其趋触及探索行为方面的改变。外周去传入可导致barrel形状及排列的可塑性变化。     

Maternal adrenalectomy affects development of adrenal medulla

This work investigates the effects of maternal adrenalectomy (ADX) on the development of the adrenal medulla. Adrenal catecholamines (AC) were measured at postnatal day (PN) 1, 8, 12 and 22 in rat offspring of ADX dams and in pups of control dams. The pups of ADX rats showed a reduction in AC concentrations in the adrenal medulla at PN 1, 12 and 22, although these were higher than in the pups of sham dams at PN 8. Further, in the pups of control mothers, there was an increase in ACs during the first two weeks of life whereas pups of ADX mothers only showed increases in noradrenaline, dopamine and adrenaline levels at day 8. These results suggest that maternal absence of corticosterone affects the medulla catecholamine content during development. These data support the idea that a maternal glucocorticoids are involved in the differentiation or/and maturation of the adrenal medulla.     

Temporal organization of multi-whisker contact in rats

Previous work has established that during exploration and discrimination, rats move their whiskers at frequencies between 6 and 12 Hz and that whisking frequency changes during contact. One critical component of any tactile system is contact. In the rat whisker system, such contacts may involve one or more vibrissa in the whisker array and contact duration of each whisker may vary over a considerable range, depending upon the behavioral context. However, little is known about the variables controlling contact duration or about the temporal relationships among contacts by adjacent whiskers. To address these issues head fixed rats were trained to touch a piezo-contact-sensor with the shaft of their whiskers (Bermejo and Zeigler, Somatosens Mot Res 17: 373-377, 2000 ). During the task, whisker movements and contacts were monitored with a high-speed camera at 500 frames/s and stored on videotape. To facilitate analysis, animals had their whiskers selectively trimmed. Data are reported from animals with C1 & C2, D1 & D2, or Arc2 (E2, D2, C2, B2) whiskers intact. For both row and arc animals, when just a single whisker touched the sensor the duration of contact was significantly shorter than when multiple whiskers made contact. When multiple whiskers made contact, onset was rarely simultaneous. Furthermore, in row-intact animals, contact progressed in an orderly fashion such that the rostral whisker in a row made contact first followed 24 ms (SE = 1.9 ms) later by the caudal whisker. When contact reversed the caudal whisker lifted off first, followed by the rostral whisker. Thus, the order in which whiskers touch an object regulates contact duration: the first whisker to touch the sensor stays in contact longer than any other whisker. The temporal discharge properties of neurons in the trigeminal system are expected to reflect position of whiskers on the nose.     

Temporal organization of multi-whisker contact in rats

Previous work has established that during exploration and discrimination, rats move their whiskers at frequencies between 6 and 12 Hz and that whisking frequency changes during contact. One critical component of any tactile system is contact. In the rat whisker system, such contacts may involve one or more vibrissa in the whisker array and contact duration of each whisker may vary over a considerable range, depending upon the behavioral context. However, little is known about the variables controlling contact duration or about the temporal relationships among contacts by adjacent whiskers. To address these issues head fixed rats were trained to touch a piezo-contact-sensor with the shaft of their whiskers (Bermejo and Zeigler, Somatosens Mot Res 17: 373-377, 2000). During the task, whisker movements and contacts were monitored with a high-speed camera at 500 frames/s and stored on videotape. To facilitate analysis, animals had their whiskers selectively trimmed. Data are reported from animals with C1 & C2, D1 & D2, or Arc2 (E2, D2, C2, B2) whiskers intact. For both row and arc animals, when just a single whisker touched the sensor the duration of contact was significantly shorter than when multiple whiskers made contact. When multiple whiskers made contact, onset was rarely simultaneous. Furthermore, in row-intact animals, contact progressed in an orderly fashion such that the rostral whisker in a row made contact first followed 24 ms (SE = 1.9 ms) later by the caudal whisker. When contact reversed the caudal whisker lifted off first, followed by the rostral whisker. Thus, the order in which whiskers touch an object regulates contact duration: the first whisker to touch the sensor stays in contact longer than any other whisker. The temporal discharge properties of neurons in the trigeminal system are expected to reflect position of whiskers on the nose.     

Serotonin regulates rhythmic whisking

Many rodents explore their environment by rhythmically palpating objects with their mystacial whiskers. These rhythmic whisker movements ("whisking"; 5-9 Hz) are thought to be regulated by an unknown brainstem central pattern generator (CPG). We tested the hypothesis that serotonin (5-HT) inputs to whisking facial motoneurons (wFMNs) are part of this CPG. In response to exogenous serotonin, wFMNs recorded in vitro fire rhythmically at whisking frequencies, and selective 5-HT2 or 5-HT3 receptor antagonists suppress this rhythmic firing. In vivo, stimulation of brainstem serotonergic raphe nuclei evokes whisker movements. Unilateral infusion of selective 5-HT2 or 5-HT3 receptor antagonists suppresses ipsilateral whisking and substantially alters the frequencies and symmetry of whisker movements. These findings suggest that serotonin is both necessary and sufficient to generate rhythmic whisker movements and that serotonergic premotoneurons are part of a whisking CPG.     

Neurobiology of secure infant attachment and attachment despite adversity: a mouse model

Attachment to an abusive caregiver has wide phylogenetic representation, suggesting that animal models are useful in understanding the neural basis underlying this phenomenon and subsequent behavioral outcomes. We previously developed a rat model, in which we use classical conditioning to parallel learning processes evoked during secure attachment (odor‐stroke, with stroke mimicking tactile stimulation from the caregiver) or attachment despite adversity (odor‐shock, with shock mimicking maltreatment). Here we extend this model to mice. We conditioned infant mice (postnatal day (PN) 7–9 or 13–14) with presentations of peppermint odor and either stroking or shock. We used ¹⁴C 2‐deoxyglucose (2‐DG) to assess olfactory bulb and amygdala metabolic changes following learning. PN7‐9 mice learned to prefer an odor following either odor‐stroke or shock conditioning, whereas odor‐shock conditioning at PN13‐14 resulted in aversion/fear learning. 2‐DG data indicated enhanced bulbar activity in PN7‐9 preference learning, whereas significant amygdala activity was present following aversion learning at PN13‐14. Overall, the mouse results parallel behavioral and neural results in the rat model of attachment, and provide the foundation for the use of transgenic and knockout models to assess the impact of both genetic (biological vulnerabilities) and environmental factors (abusive) on attachment‐related behaviors and behavioral development .     

Whisker plucking alters responses of rat trigeminal ganglion neurons

Whisker plucking in developing and adult rats provides a convenient method of temporarily altering tactile input for the purposes of studying experience-dependent plasticity in the somatosensory cortex. Yet, a comprehensive examination of the effect of whisker plucking on the response properties of whisker follicle-innervating trigeminal ganglion (NVg) neurons is lacking. We used extracellular single unit recordings to examine responses of NVg neurons to controlled whisker stimuli in three groups of animals: (1) rats whose whiskers were plucked from birth for 21 days; (2) rats whose whiskers were plucked once at 21 days of age; and (3) control animals. After at least 3 weeks of whisker re-growth, NVg neurons in plucked rats displayed normal, single whisker receptive fields and could be characterized as slowly (SA) or rapidly adapting (RA). The proportion of SA and RA neurons was unaffected by whisker plucking. Both SA and RA NVg neurons in plucked rats displayed normal response latencies and angular tuning but abnormally large responses to whisker movement onsets and offsets. SA neurons were affected to a greater extent than RA neurons. The effect of whisker plucking was more pronounced in animals whose whiskers were plucked repeatedly during development than in rats whose whiskers were plucked once. Individual neurons in plucked animals displayed abnormal periods of prolonged rhythmic firing following deflection onsets and aberrant bursts of activity during the plateau phase of the stimulus. These results indicate that whisker plucking exerts a long-term effect on responses of trigeminal ganglion neurons to peripheral stimulation.     

Whisker plucking alters responses of rat trigeminal ganglion neurons

Whisker plucking in developing and adult rats provides a convenient method of temporarily altering tactile input for the purposes of studying experience-dependent plasticity in the somatosensory cortex. Yet, a comprehensive examination of the effect of whisker plucking on the response properties of whisker follicle-innervating trigeminal ganglion (NVg) neurons is lacking. We used extracellular single unit recordings to examine responses of NVg neurons to controlled whisker stimuli in three groups of animals: (1) rats whose whiskers were plucked from birth for 21 days; (2) rats whose whiskers were plucked once at 21 days of age; and (3) control animals. After at least 3 weeks of whisker re-growth, NVg neurons in plucked rats displayed normal, single whisker receptive fields and could be characterized as slowly (SA) or rapidly adapting (RA). The proportion of SA and RA neurons was unaffected by whisker plucking. Both SA and RA NVg neurons in plucked rats displayed normal response latencies and angular tuning but abnormally large responses to whisker movement onsets and offsets. SA neurons were affected to a greater extent than RA neurons. The effect of whisker plucking was more pronounced in animals whose whiskers were plucked repeatedly during development than in rats whose whiskers were plucked once. Individual neurons in plucked animals displayed abnormal periods of prolonged rhythmic firing following deflection onsets and aberrant bursts of activity during the plateau phase of the stimulus. These results indicate that whisker plucking exerts a long-term effect on responses of trigeminal ganglion neurons to peripheral stimulation.     

胡须信息在大鼠双侧初级体感皮层间的传递路径

大鼠的初级体感皮层(primary somatosensory cortex,SⅠ)虽然只接受来自对侧胡须的上行输入,但仍可以被同侧胡须刺激所激活.解剖学研究发现,在两侧SⅠ皮层之间有两条传递胡须信息胼胝体通路:一条是类颗粒区(perigranular zone,PGZ)通路;另一条是异颗粒区(dysgranular zone,DZ)通路.然而,哪一条通路在传递胡须刺激信息的过程中起主要作用还不清楚.本研究使用电压敏感染料(voltage-sensitive dye,VSD)成像技术来观察胡须刺激时整个SⅠ的神经元群体活动的空间分布和时间特性.实验发现,对侧胡须刺激首先激活barrel(颗粒区,granular zone,GZ),然后以兴奋波的形式传播到胡须感觉区(sub-barrel field cortex,BFC)外侧的DZ.而与首先激活BFC的对侧胡须刺激不同,同侧胡须刺激首先激活SⅠ的DZ.所激发的皮层兴奋以波的形式传播并扩散至BFC.失活另一侧皮层可以抑制这种同侧反应.电刺激另一侧半球皮层与刺激同侧胡须类似,也首先激活成像侧DZ.我们的实验结果显示,胡须刺激激活对侧SⅠ,在经过胼胝体传导后,另一侧半球的DZ(同侧于被刺激的胡须)被激活.连接双侧皮层DZ区的胼胝体连接在SⅠ对同侧胡须刺激的反应中起了主导作用.     

Thermoregulation in rats during early postnatal maturation: importance of nitric oxide

Experiments were carried out to determine the role of nitric oxide in mediating autonomic and behavioral thermoregulatory control in rat pups on postnatal days 1-2, 5-6, and 10-11. For an experiment, each pup received a subcutaneous injection of vehicle, NG-nitro-D-arginine methyl ester (D-NAME; 100 mg/kg), or NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg) before being placed in a metabolic chamber or in a thermocline with a linear temperature gradient of 23 to 43 degrees C. In the metabolic chamber, oxygen consumption and core temperature were measured as ambient temperature was decreased from 40 to 15 degrees C over a 60-min period. Decreasing ambient temperature elicited an increase in oxygen consumption in all age groups that received vehicle or d-NAME. The lower critical temperature and peak oxygen consumption upon exposure to cold after vehicle were 41 +/- 10 ml x kg(-1) x min(-1) at 30 degrees C, 43 +/- 12 ml x kg(-1) x min(-1) at 28 degrees C, and 55 +/- 11 ml x kg(-1) x min(-1) at 25 degrees C in the 1- to 2-, 5- to 6-, and 10- to 11-day-old pups, respectively. Administration of L-NAME abolished the oxygen consumption response to cold in the 1- to 2- and 5- to 6-day-old pups and significantly attenuated the oxygen consumption response to cold in the 10- to 11-day-old pups. Selected ambient temperature in the thermocline was not significantly affected by prior administration of D-NAME or L-NAME compared with vehicle. Thus our data provide evidence that the nitric oxide system plays a role in mediating autonomic but not behavioral thermoregulatory control in rat pups during early postnatal maturation.     

Use-dependent plasticity in barrel cortex: Intrinsic signal imaging reveals functional expansion of spared whisker representation into adjacent deprived columns

We used optical imaging of intrinsic cortical signals, elicited by whisker stimulation, to define areas of activation in primary sensory cortex of normal hamsters and hamsters subjected to neonatal follicle ablation at postnatal day seven (P7). Follicle ablations were unilateral, and spared either C-row whiskers or the second whisker arc. This study was done to determine if the intrinsic cortical connectivity pattern of the barrel cortex, established during the critical period, affects the process of representational plasticity that follows whisker follicle ablation. Additionally, we tested the ability to monitor such changes in individual cortical whisker representations using intrinsic signal imaging. Stimulation of a single whisker yielded peak activation of a barrel-sized patch in the somatotopically appropriate location in normal cortex. In both row and arc-spared animals, functional representations corresponding to spared follicles were significantly stronger and more oblong than normal. The pattern of activation differed in the row-sparing and arc-sparing groups, in that the expansion was preferentially into deprived, not spared areas. Single whisker stimulation in row-spared cases preferentially activated the corresponding barrel arc, while stimulation of one whisker in arc-spared cases produced elongated activation down the barrel row. Since whisker deflection normally has a net inhibitory effect on neighboring barrels, our data suggest that intracortical inhibition fails to develop normally in deprived cortical columns. Because thalamocortical projections are not affected by follicle ablation after P7, we suggest that the effects we observed are largely cortical, not thalamocortical.     

Use-dependent plasticity in barrel cortex: intrinsic signal imaging reveals functional expansion of spared whisker representation into adjacent deprived columns

We used optical imaging of intrinsic cortical signals, elicited by whisker stimulation, to define areas of activation in primary sensory cortex of normal hamsters and hamsters subjected to neonatal follicle ablation at postnatal day seven (P7). Follicle ablations were unilateral, and spared either C-row whiskers or the second whisker arc. This study was done to determine if the intrinsic cortical connectivity pattern of the barrel cortex, established during the critical period, affects the process of representational plasticity that follows whisker follicle ablation. Additionally, we tested the ability to monitor such changes in individual cortical whisker representations using intrinsic signal imaging. Stimulation of a single whisker yielded peak activation of a barrel-sized patch in the somatotopically appropriate location in normal cortex. In both row and arc-spared animals, functional representations corresponding to spared follicles were significantly stronger and more oblong than normal. The pattern of activation differed in the row-sparing and arc-sparing groups, in that the expansion was preferentially into deprived, not spared areas. Single whisker stimulation in row-spared cases preferentially activated the corresponding barrel arc, while stimulation of one whisker in arc-spared cases produced elongated activation down the barrel row. Since whisker deflection normally has a net inhibitory effect on neighboring barrels, our data suggest that intracortical inhibition fails to develop normally in deprived cortical columns. Because thalamocortical projections are not affected by follicle ablation after P7, we suggest that the effects we observed are largely cortical, not thalamocortical.     

Development of rodent macrovibrissae: Effects of neonatal whisker denervation and bilateral neonatal enucleation

In this paper we describe the effects of manipulating two kinds of sensory input in neonatal rats upon the development of the macrovibrissae—that movable subset of the rodent mystacial vibrissae. In an initial study of normal whisker development, data on whisker size were obtained from neonatal, perinatal, and adult rats. Data on whisker size were also obtained from rats sustaining either neonatal sensory or motor denervation of the whiskers and from both rats and mice bilaterally enucleated as neonates (BEN). In normally reared rats, most whiskers attain their final size over the first three postnatal weeks but development of rows 6 and 7 are not completed until after the first month. In normal animals we found a significant correlation both between body weight and whisker size and between the size of a whisker and the size of its corresponding cortical barrel. Rats sustaining neonatal denervation of the whiskers have shorter and thinner whiskers as adults than normally reared animals. In both rats and mice bilaterally enucleated as neonates a subset of the macrovibrissae are significantly larger than those of normal controls but no such effect is seen if the enucleation is carried out in adults. Moreover, BEN rats exposed to a novel stimulus environment whisk at a significantly higher frequency than normally reared animals. Mechanisms which might mediate these effects are discussed.     

Caspase-3 and calpain activities after acute and repeated ethanol administration during the rat brain growth spurt

Ethanol administration during the rat brain growth spurt triggers apoptotic neurodegeneration that appears to be mediated by caspase-3 activation. In order to gain more insight on the role of this caspase in ethanol-induced developmental neurotoxicity, we studied its expression and activity under different conditions of ethanol exposure during development. Furthermore, because of the cross-talk between caspase-3 and calpain we extended our study also at this protease. Ethanol was administered by gavage to rat pups as a single-day exposure on postnatal day (PN) 7 or from PN4 to PN10. Cleaved caspase-3 expression peaked in the cerebral cortex 12 h after ethanol treatment and returned to control values at 24 h. An identical pattern was found for caspase-3-like activity, that was increased only with the highest dose of ethanol tested (5 g/kg) and mostly in PN4. Repeated ethanol exposure, at a dose that was previously found to induce microencephaly, did not increase caspase-3 expression and activity although it decreased procaspase-3 expression and released mitochondrial cytochrome c. Repeated ethanol administration also increased calpain activity. These data show that acute and repeated ethanol administration differentially affect caspase-3 and calpain activity, suggesting that calpain activation may play a role in developmental neurotoxicity of ethanol.     

Maternal attenuation of hypothalamic paraventricular nucleus norepinephrine switches avoidance learning to preference learning in preweanling rat pups

Infant rats learn to prefer stimuli paired with pain, presumably due to the importance of learning to prefer the caregiver to receive protection and food. With maturity, a more 'adult-like' learning system emerges that includes the amygdala and avoidance/fear learning. The attachment and 'adult-like' systems appear to co-exist in older pups with maternal presence engaging the attachment system by lowering corticosterone (CORT). Specifically, odor-shock conditioning (11 odor-0.5 mA shock trials) in 12-day-old pups results in an odor aversion, although an odor preference is learned if the mother is present during conditioning. Here, we propose a mechanism to explain pups ability to 'switch' between the dual learning systems by exploring the effect of maternal presence on hypothalamic paraventricular nucleus (PVN) neural activity, norepinephrine (NE) levels and learning. Maternal presence attenuates both PVN neural activity and PVN NE levels during odor-shock conditioning. Intra-PVN NE receptor antagonist infusion blocked the odor aversion learning with maternal absence, while intra-PVN NE receptor agonist infusion permitted odor aversion learning with maternal presence. These data suggest maternal control over pup learning acts through attenuation of PVN NE to reduce the CORT required for pup odor aversion learning. Moreover, these data also represent pups' continued maternal dependence for nursing, while enabling aversion learning outside the nest to prepare for pups future independent living.     

Supplementation of suckling rats with cow's milk induces hyperphagia and higher visceral adiposity in females at adulthood,but not in males

In humans, complementary feeding should be started after 6 months-old; the introduction of any food or water before this time is considered early weaning, which is associated with health problems in adulthood. Cow's milk is a common food introduced to children less than 6 months that has inadequate nutritional composition mainly due to a worse casein: whey protein ratio compared to human milk. We hypothesized that suckling rats fed with cow's milk, rich in bioactive peptides, develop further metabolic dysfunctions. From postnatal day (PN) 14 to 20, Wistar rat pups were divided into 3 groups: rat milk (RM) – pups received rat milk orally in a syringe; cow's milk (CM), pups received cow's milk; CM with high protein (CM-H), CM with twice protein amount of rat milk. Pups were killed on PN21 and PN180. At PN21, CM males had lower visceral fat mass compared with other groups. Serum corticosterone was higher in CM-H males, despite no change in glucocorticoid metabolism in liver and visceral fat. At PN180, CM and CM-H females had greater fat depots and hyperphagia, although no alteration in leptinemia and leptin signaling in hypothalamus. CM-H females had a trend of hypoinsulinemia and significant decrease in HOMA-β, suggesting lower insulin secretion. Males from CM-H group had only lower total body protein mass. CM males had hypercorticosteronemia associated with lower expression of 11βHDS1 in visceral fat. In conclusion, early introduction of cow's milk in neonate rats leads to gender-dependent differences in metabolic and endocrine parameters in the short- and long-term.     

Transient changes of cortical interhemispheric responses after repeated caffeine administration in immature rats

Repeated postnatal caffeine treatment of rat pups led to transient developmental changes in cortical epileptic afterdischarges. To know if physiological cortical functions are also affected transcallosal evoked potentials were studied. Rat pups of the Wistar strain were injected daily with caffeine (10 or 20 mg/kg s.c.) from postnatal day (P) 7 to P11, control siblings received saline. Cortical interhemispheric responses were tested at P12, 18, 25 and in young adult rats. Amplitude of initial monosynaptic components was evaluated in averaged responses. Single pulses as well as paired and frequency (five pulses) stimulations were used. Developmental rules - highest amplitude of responses in 25-day-old rats, potentiation with paired and frequency stimulation present since P18 - were confirmed. Caffeine-treated rats exhibited transient changes: single responses were augmented in P25 if high stimulation intensity was used, paired-pulse and frequency responses were higher in experimental than in control animals at P12, the opposite change was observed in 18- and more markedly in 25-day-old rats. No significant changes were found in adult animals, monosynaptic transcallosal responses represent a simple and robust system. The developmental profile of described changes did not exactly correspond to changes in epileptic afterdischarges supporting the possibility that afterdischarges did not arise from early monosynaptic components of responses. In spite of transient nature of changes they can reflect delayed or more probably modified brain development.