Weak and nondiscriminative responses to conspecifics in the rat hippocampus.

Little is known about how hippocampal neurons in rodents respond to and represent conspecifics. To address this question, we let rats interact while quantifying hippocampal neuronal activation patterns with extracellular recordings and immediate-early gene (c-Fos) expression. A total of 319 single putative pyramidal neurons was recorded in dorsal hippocampus. In sessions with multiple stimulus rats, no cell responded differentially to individual rats (N = 267 cells). We did find, however, that the presence of other rats induced a significant enhancement or suppression of firing in a fraction of neurons (n = 22 of 319; 7%). As expected, a large fraction of neurons (n = 170; 53%) had place fields. There was no evidence for place-independent responses to rats. Rather, the modulations were linked to the spatial responses. While neurons did not discriminate between individual rats, they did discriminate between rats and inanimate objects. Surprisingly, neuronal responses were more strongly modulated by objects than by rats, even though subjects spent more time near their conspecifics. Consistent with the low fraction of rat-modulated cells, social encounters did not induce c-Fos expression in the hippocampus, while there was a social interaction-specific expression in the basolateral amygdala. In both interacting and non-interacting rats, the fraction of c-Fos-expressing cells in the hippocampus was very low. Our investigation of social coding in the rat hippocampus, along with other recent work, showed that social responses were rare and lacked individual specificity, altogether speaking against a role of rodent dorsal hippocampus in social memory.

Highly structured, partner-sex- and subject-sex-dependent cortical responses during social facial touch.

Touch is a fundamental aspect of social, parental and sexual behavior. In contrast to our detailed knowledge about cortical processing of non-social touch, we still know little about how social touch impacts cortical circuits. We investigated neural activity across five frontal, motor and sensory cortical areas in rats engaging in naturalistic social facial touch. Information about social touch and the sex of the interaction partner (a biologically significant feature) is a major determinant of cortical activity. 25.3% of units were modulated during social touch and 8.3% of units displayed 'sex-touch' responses (responded differently, depending on the sex of the interaction partner). Single-unit responses were part of a structured, partner-sex- and, in some cases, subject-sex-dependent population response. Spiking neural network simulations indicate that a change in inhibitory drive might underlie these population dynamics. Our observations suggest that socio-sexual characteristics of touch (subject and partner sex) widely modulate cortical activity and need to be investigated with cellular resolution.

Neuronal Responses to Conspecifics in the Ventral CA1.

Conspecific recognition and discrimination is a vital aspect of social interactions. Genetic manipulations have implicated the CA2 sub-field and ventral hippocampus in rodent social memory. However, little is known about the nature of hippocampal responses to social signals. We characterized ventral CA1 responses in rats while interacting with conspecifics across a gap. Many cells showed unusual "social presence responses," i.e., large elevations of firing rates, which were contingent on the presence of a conspecific. Sharp-wave ripple activity was also increased by conspecific presence. The cells were modulated by facial touch and ultrasonic vocalizations. In male rats, female conspecifics evoked stronger responses than males. In addition, responses to females differed more strongly between individual females than between males. Cells showed little response to object presence. Ventral CA1 responses were also markedly different from those of dorsal CA1, where most cells were weakly inhibited by conspecific presence.

Embryo-endometrial expression of leukemia inhibitory factor in the golden hamster (Mesocricetus auratus): increased expression during proestrous and window of implantation stages.

Leukemia inhibitory factor (LIF) is a pleiotropic IL-6 family cytokine and its maternal uterine expression is critical for mouse blastocyst implantation. In the golden hamster (Mesocricetus auratus), although the blastocyst hatching phenomenon is quite interesting and LIF is shown to regulate hatching, information is not available on the embryonic and uterine expression of LIF and hormonal regulation of LIF expression during the peri-implantation period. The present investigation is aimed at studying embryonic and uterine expression of LIF during preimplantation hamster development. We observed embryonic expression of LIF mRNA and protein in the 8-cell, morula and blastocyst stages. In cycling females, uterine LIF mRNA expression was maximal during the oestrogen-dominant phase of the oestrous cycle, i.e. proestrous stage. Interestingly, during pregnancy, both LIF mRNA and protein were highly upregulated on Days 3.5 and 4 ('window of implantation'), implying a role for this cytokine in blastocyst hatching and implantation. Cell type-specific localisation of LIF mRNA and protein was observed predominantly in luminal epithelium and uterine glands with faint staining being detected in the stroma. The hamster uterus encoded a approximately 4.2 kb LIF transcript whose coding region, when cloned and sequenced, showed a high degree of identity to the murine cDNA counterpart. These data demonstrate that: (1) hamster preimplantation embryos show LIF mRNA and protein expression; (2) uterine expression of LIF mRNA and protein was dependent on elevated levels of circulating oestrogen, and (3) there is a possible functional association of LIF with the peri-implantation development in the golden hamster.

Socio-sexual processing in cortical circuits.

How does social and sexual information processing map onto cortical circuits? Addressing this question has been difficult, because of a lack of circuit-oriented social neuroscience and an absence of measurements from interacting brains. Recent work showed social information is already differentially processed in the primary sensory cortices. Converging evidence suggests that prefrontal areas contribute to social interaction processing and determining social hierarchies. In social interactions, we identify gender in split seconds, but after centuries of anatomy we are still unable to distinguish male and female cortices. Novel data reinforce the idea of a bisexual layout of cortical anatomy. Physiological analysis, however, provided evidence for sex differences in cortical processing. Unlike other cortical circuits, sexual processing circuits undergo major rewiring and expansion during puberty and show lasting damage from childhood abuse.

The representation of social facial touch in rat barrel cortex.

Controlled presentation of stimuli to anesthetized [1] or awake [2] animals suggested that neurons in sensory cortices respond to elementary features [3, 4], but we know little about neuronal responses evoked by social interactions. Here we investigate processing in the barrel cortex of rats engaging in social facial touch [5, 6]. Sensory stimulation by conspecifics differs from classic whisker stimuli such as deflections, contact poles [7, 8], or textures [9, 10]. A large fraction of barrel cortex neurons responded to facial touch. Social touch responses peaked when animals aligned their faces and contacted each other by multiple whiskers with small, irregular whisker movements. Object touch was associated with larger, more regular whisker movements, and object responses were weaker than social responses. Whisker trimming abolished responses. During social touch, neurons in males increased their firing on average by 44%, while neurons in females increased their firing by only 19%. In females, socially evoked and ongoing firing rates were more than 1.5-fold higher in nonestrus than in estrus. Barrel cortex represented socially different contacts by distinct firing rates, and the variation of activity with sex and sexual status could contribute to the generation of gender-specific neural constructs of conspecifics.

Vocalization-whisking coordination and multisensory integration of social signals in rat auditory cortex.

Social interactions involve multi-modal signaling. Here, we study interacting rats to investigate audio-haptic coordination and multisensory integration in the auditory cortex. We find that facial touch is associated with an increased rate of ultrasonic vocalizations, which are emitted at the whisking rate (∼8 Hz) and preferentially initiated in the retraction phase of whisking. In a small subset of auditory cortex regular-spiking neurons, we observed excitatory and heterogeneous responses to ultrasonic vocalizations. Most fast-spiking neurons showed a stronger response to calls. Interestingly, facial touch-induced inhibition in the primary auditory cortex and off-responses after termination of touch were twofold stronger than responses to vocalizations. Further, touch modulated the responsiveness of auditory cortex neurons to ultrasonic vocalizations. In summary, facial touch during social interactions involves precisely orchestrated calling-whisking patterns. While ultrasonic vocalizations elicited a rather weak population response from the regular spikers, the modulation of neuronal responses by facial touch was remarkably strong.

Glucocorticoids protect against the delayed behavioral and cellular effects of acute stress on the amygdala.

BACKGROUND: A single episode of acute immobilization stress has previously been shown to trigger a delayed onset of anxiety-like behavior and spinogenesis in the basolateral amygdala (BLA) of rats. Spurred on by a seemingly paradoxical observation in which even a modest increase in corticosterone (CORT), caused by a single vehicle injection before stress, could dampen the delayed effects of stress, we hypothesized a protective role for glucocorticoids against stress. METHODS: We tested this hypothesis by analyzing how manipulations in CORT levels modulate delayed increase in anxiety-like behavior of rats on the elevated plus-maze 10 days after acute stress. We also investigated the cellular correlates of different levels of anxiety under different CORT conditions by quantifying spine density on Golgi-stained BLA principal neurons. RESULTS: CORT in drinking water for 12 hours preceding acute stress prevented delayed increase in anxiety rather than exacerbating it. Conversely, vehicle injection failed to prevent the anxiogenic effect of stress in bilaterally adrenalectomized rats. However, when CORT was restored in adrenalectomized rats by injection, the delayed anxiogenic effect of stress was once again blocked. Finally, high and low anxiety states were accompanied by high and low levels of BLA spine density. CONCLUSIONS: Our findings suggest that the presence of elevated levels of CORT at the time of acute stress confers protection against the delayed enhancing effect of stress on BLA synaptic connectivity and anxiety-like behavior. These observations are consistent with clinical reports on the protective effects of glucocorticoids against the development of posttraumatic symptoms triggered by traumatic stress.

Cellular and molecular regulation of mammalian blastocyst hatching.

In mammals including humans, failure in blastocyst hatching and implantation leads to early embryonic loss and infertility. Prior to implantation, the blastocyst must hatch out of its acellular glycoprotein coat, the zona pellucida (ZP). The phenomenon of blastocyst hatching is believed to be regulated by (i) dynamic cellular components such as actin-based trophectodermal projections (TEPs), and (ii) a variety of autocrine and paracrine molecules such as growth factors, cytokines and proteases. The spatio-temporal regulation of zona lysis by blastocyst-derived cellular and molecular signaling factors is being keenly investigated. Our studies show that hamster blastocyst hatching is accelerated by growth factors such as heparin binding-epidermal growth factor and leukemia inhibitory factor and that embryo-derived, cysteine proteases including cathepsins are responsible for blastocyst hatching. Additionally, we believe that cyclooxygenase-generated prostaglandins, estradiol-17beta mediated estrogen receptor-alpha signaling and possibly NFkappaB could be involved in peri-hatching development. Moreover, we show that TEPs are intimately involved with lysing ZP and that the TEPs potentially enrich and harbor hatching-enabling factors. These observations provide new insights into our understanding of the key cellular and molecular regulators involved in the phenomenon of mammalian blastocyst hatching, which is essential for the establishment of early pregnancy.

Expression of glucose transporter isoforms and the insulin receptor during hamster preimplantation embryo development.

During preimplantation development, embryos of many species are known to express up to five isoforms of the facilitative glucose transporter proteins (GLUT). Development of hamster blastocysts is inhibited by glucose. We therefore investigated GLUT isoform and insulin receptor (IR) expression in hamster preimplantation embryos cultured in glucose-free medium from the 8-cell stage onwards. We show that GLUT1, 3 and 8 mRNA are constitutively expressed from the 8-cell to the blastocyst stage. The IR is expressed from the morula stage onwards. Messenger RNA of the insulin-responsive GLUT4 was not detected at any stage. GLUT1 and 3 were localised by immunocytochemistry. GLUT1 was expressed in both embryoblast and trophoblast, in the latter, mainly in basal and lateral membranes directed towards the blastocoel and embryoblast. GLUT3 was exclusively localised in the apical membrane of trophoblast cells. We show that hamster preimplantation embryos express several GLUT isoforms thus closely resembling embryos of other mammalian species. Despite endogenous IR expression, the insulin-sensitive isoform GLUT4 was not expressed, indicating that the insulin-mediated glucose uptake known from classical insulin target cells may not be relevant for hamster blastocysts.