Simulação da preferência do odor maternal : da neuroetologia à biofísica

A tese é composta por dois trabalhos complementares. No primeiro trabalho, estudamos o aprendizado do odor materno em ratos neonatos, com foco no final do período sensível para o aprendizado precoce de preferência de odor. No segundo trabalho, estudamos as características das correntes GABAérgicas dos interneurônios do córtex piriforme anterior (CPa) e seu papel no aprendizado precoce de preferência de odor. Para ambos os estudos, foram usados dados eletrofisiológicos experimentais e modelos computacionais foram desenhados usando modelagem baseada em agentes. Os resultados são descritos como o número acumulado de spikes e número de neurônios ativos, antes e depois do condicionamento. No primeiro artigo, mostramos que as mudanças nas propriedades intrínsecas das células piramidais no CPa reduzem a disponibilidade de células piramidais que respondem à exposição do odor materno. No segundo artigo, experimentos computacionais mostraram que a entrada GABAérgica no CPa melhora a habilidade do circuito olfatório para o aprendizado do odor materno. A discussão geral apresenta uma integração dos níveis da neuroetologia à biofísica como uma perspectiva de trabalho.The thesis consists of two complementary studies. In the first study, we investigated the maternal odor learning in neonatal rats, focusing on the end of the sensitive period for early odor preference learning. In the second study, we examined the characteristics of the GABAergic currents of the interneurons of the anterior piriform cortex (aPC) and their role in early odor preference learning. For both studies, experimental electrophysiological data were used, and computational models were designed using agent-based modeling. The results are described as the cumulative number of spikes and the number of active neurons, before and after conditioning. In the first article, we showed that changes in the intrinsic properties of aPC pyramidal cells reduced the availability of the responsive pyramidal cells during maternal odor exposure. In the second article, computational experiments showed that GABAergic entry into the aPC improves the olfactory circuit's ability to learn maternal odor. The general discussion presents an integration of the levels from neuroethology to biophysics as a work perspective

The maturational characteristics of the GABA input in the anterior piriform cortex may also contribute to the rapid learning of the maternal odor during the sensitive period

During the first ten postnatal days (P), infant rodents can learn olfactory preferences for novel odors if they are paired with thermo-tactile stimuli that mimic components of maternal care. After P10, the thermo-tactile pairing becomes ineffective for conditioning. The current explanation for this change in associative learning is the alteration in the norepinephrine (NE) inputs from the locus coeruleus (LC) to the olfactory bulb (OB) and the anterior piriform cortex (aPC). By combining patchclamp electrophysiology and computational simulations, we showed in a recent work that a transitory high responsiveness of the OB-aPC circuit to the maternal odor is an alternative mechanism that could also explain early olfactory preference learning and its cessation after P10. That result relied solely on the maturational properties of the aPC pyramidal cells. However, the GABAergic system undergoes important changes during the same period. To address the importance of the maturation of the GABAergic system for early olfactory learning, we incorporated data from the GABA inputs, obtained from in vitro patch-clamp experiment in the aPC of rat pups aged P5–P7 reported here, to the model proposed in our previous publication. In the younger than P10 OB-aPC circuit with GABA synaptic input, the number of responsive aPC pyramidal cells to the conditioned maternal odor was amplified in 30% compared to the circuit without GABAergic input. When compared with the circuit with other younger than P10 OB-aPC circuit with adult GABAergic input profile, this amplification was 88%. Together, our results suggest that during the olfactory preference learning in younger than P10, the GABAergic synaptic input presumably acts by depolarizing the aPC pyramidal neurons in such a way that it leads to the amplification of the pyramidal neurons response to the conditioned maternal odor. Furthermore, our results suggest that during this developmental period, the aPC pyramidal cells themselves seem to resolve the apparent lack of GABAergic synaptic inhibition by a strong firing adaptation in response to increased depolarizing inputs

Maturation of pyramidal cells in anterior piriform cortex may be sufficient to explain the end of early olfactory learning in rats

Studies have shown that neonate rodents exhibit high ability to learn a preference for novel odors associated with thermotactile stimuli that mimics maternal care. Artificial odors paired with vigorous strokes in rat pups younger than 10 postnatal days (P), but not older, rapidly induce an orientation-approximation behavior toward the conditioned odor in a two-choice preference test. The olfactory bulb (OB) and the anterior olfactory cortex (aPC), both modulated by norepinephrine (NE), have been identified as part of a neural circuit supporting this transitory olfactory learning. One possible explanation at the neuronal level for why the odor-stroke pairing induces consistent orientation-approximation behavior in P10, is the coincident activation of prior existent neurons in the aPC mediating this behavior. Specifically, odorstroke conditioning in P10 pups, promoting orientation-approximation behavior in the former but not in the latter. In order to test this hypothesis, we performed in vitro patch-clamp recordings of the aPC pyramidal neurons from rat pups from two age groups (P5–P8 and P14–P17) and built computational models for the OB-aPC neural circuit based on this physiological data. We conditioned the P5–P8 OB-aPC artificial circuit to an odor associated with NE activation (representing the process of maternal odor learning during mother–infant interactions inside the nest) and then evaluated the response of the OB-aPC circuit to the presentation of the conditioned odor. The results show that the number of responsive aPC neurons to the presentation of the conditioned odor in the P14–P17 OB-aPC circuit was lower than in the P5–P8 circuit, suggesting that at P14–P17, the reduced number of responsive neurons to the conditioned (maternal) odor might not be coincident with the responsive neurons for a second conditioned odor

Simulação da preferência do odor maternal : da neuroetologia à biofísica

A tese é composta por dois trabalhos complementares. No primeiro trabalho, estudamos o aprendizado do odor materno em ratos neonatos, com foco no final do período sensível para o aprendizado precoce de preferência de odor. No segundo trabalho, estudamos as características das correntes GABAérgicas dos interneurônios do córtex piriforme anterior (CPa) e seu papel no aprendizado precoce de preferência de odor. Para ambos os estudos, foram usados dados eletrofisiológicos experimentais e modelos computacionais foram desenhados usando modelagem baseada em agentes. Os resultados são descritos como o número acumulado de spikes e número de neurônios ativos, antes e depois do condicionamento. No primeiro artigo, mostramos que as mudanças nas propriedades intrínsecas das células piramidais no CPa reduzem a disponibilidade de células piramidais que respondem à exposição do odor materno. No segundo artigo, experimentos computacionais mostraram que a entrada GABAérgica no CPa melhora a habilidade do circuito olfatório para o aprendizado do odor materno. A discussão geral apresenta uma integração dos níveis da neuroetologia à biofísica como uma perspectiva de trabalho.The thesis consists of two complementary studies. In the first study, we investigated the maternal odor learning in neonatal rats, focusing on the end of the sensitive period for early odor preference learning. In the second study, we examined the characteristics of the GABAergic currents of the interneurons of the anterior piriform cortex (aPC) and their role in early odor preference learning. For both studies, experimental electrophysiological data were used, and computational models were designed using agent-based modeling. The results are described as the cumulative number of spikes and the number of active neurons, before and after conditioning. In the first article, we showed that changes in the intrinsic properties of aPC pyramidal cells reduced the availability of the responsive pyramidal cells during maternal odor exposure. In the second article, computational experiments showed that GABAergic entry into the aPC improves the olfactory circuit's ability to learn maternal odor. The general discussion presents an integration of the levels from neuroethology to biophysics as a work perspective