Electrophysiological evidence for change detection in speech sound patterns by anesthetized rats

Peer reviewe

Uudistav käitumine ning 50-kHz ultrahelihäälitsused rottidel: indiviididevaheliste erinevuste käitumuslikud ja neurokeemilised profiilid

Affective disorders, including depression and anxiety disorders are a major cause of disability in the world. The biological basis of affective disorders as well as the relationship between the pharmacological profiles and therapeutic effects of antidepressants still lack a coherent theory. One reason for this is the relative lack of adequate animal models for studies of neurobiological basis of these disorders. The main aim of the present studies was development of two potential models of affective states that were based on exploratory behaviour and ultrasonic vocalizations in rats. Exploratory behaviour is influenced by fear and curiosity towards novel objects and environments, and many behavioural tests hence use it as a measure for anxiety. The 50-kHz ultrasonic vocalizations emitted by rats have been associated with positively valenced conditions. Significant inter-individual variations have been previously found in both behaviours. In the present studies exploratory behaviour and 50-kHz ultrasonic vocalizations were investigated as stable individual dispositions. Methods were developed for adequate measurement of individually characteristic levels of both behaviours and behavioural and neurobiological differences between the resulting low-exploring versus high-exploring and low-chirping versus high-chirping groups were studied. It was found that low-exploring animals are more anxious and use more passive coping strategies. The differences between high- and low-exploring animals are at least in part influenced by differences in midbrain dopamine and serotonin neurotransmission in prefrontal cortex and hippocampus (with possible influences from molecules regulating transcriptional processes and neural development). Male rats who emit low levels of 50-kHz ultrasonic vocalizations show greater susceptibility to stressful stimuli which is especially expressed in chronic stress-induced changes in brain metabolic activity. In females, the animals who emit high levels of 50-kHz ultrasonic vocalizations are more sensitive to stress.Häired emotsionaalsetes protsessides, sealhulgas depressioon ning ärevushäired, on ühed olulisimad inimkonda vaevavad patoloogilised probleemid. Nende tekke ning kasutusel olevate ravimite toimemehhanismide kohta puudub ammendav teooria, mille üheks põhjuseks on adekvaatsete loommudelite nappus nende häirete neurobioloogilise aluse uurimiseks. Käesoleva töö eesmärgiks oli kahe potentsiaalse afektiivsete seisundite loommudeli väljatöötamine, mis tuginevad vastavalt uudistavale käitumisele ning ultrahelihäälitsustele rottidel. Uudistavat käitumist mõjutavad samaaegselt nii hirm kui ka uudishimu võõraste objektide suhtes, mistõttu sellel põhineb suur hulk ärevuse mõõtmisega seotud käitumisteste. Rottide poolt 50-kHz sagedusel esitatud ultrahelihäälitsuste hulk seondub positiivse valentsiga seisunditega. Mõlema tunnuse osas on varasemalt täheldatud olulist indiviididevahelist variatsiooni. Käesolevas töös uuriti nimetatud käitumisi stabiilsete püsiomadustena individuaalsetel katseloomadel. Uuringute käigus töötati välja meetodid uudistava käitumise ning 50-kHz ultrahelihäälitsuste stabiilse individuaalse taseme määramiseks ning uuriti sel alusel tekkivate vähe- ning palju-uudistavate ja vähe ning palju 50-kHz ultrahelihäälitsusi esitavate rottide käitumuslikke ning neurobioloogilisi erinevusi. Leiti, et madala uudistamisaktiivsusega loomad on ärevamad ning kasutavad passiivsemaid toimetulekustrateegiaid. Madala ning kõrge uudistamisaktiivsusega rottide vahelistes erinevustes mängivad olulist rolli erinevused keskaju dopamiinergilistes ning prefrontaalkoore ja hippokampuse serotoniinergilistes süsteemides, mida mõjutavad ka variatsioonid geenitranskriptsiooni ning neuronaalset arengut mõjustavate molekulides. Isased vähe 50-kHz ultrahelihäälitsusi tegevad loomad on tundlikumad negatiivsetele stiimulitele, mis avaldub eriti kroonilisest stressist tingitud muutustes aju metaboolses aktiivsuses. Emaste loomade hulgas on stressile tundlikumad palju 50-kHz ultrahelihäälitsusi tegevad loomad

Psüühiliste protsesside modelleerimine loomadel- Tanel Mällo

SOPH.00.270 Uurimus, andmed ja interpretatsioo

Mismatch brain response to speech sound changes in rats

Understanding speech is based on neural representations of individual speech sounds. In humans, such representations are capable of supporting an automatic and memory-based mechanism for auditory change detection, as reflected by the mismatch negativity (MMN) of event-related potentials. There are also findings of neural representations of speech sounds in animals, but it is not known whether these representations can support the change detection mechanism analogous to that underlying the MMN in humans. To this end, we presented synthesized spoken syllables to urethane-anesthetized rats while local field potentials were epidurally recorded above their primary auditory cortex. In an oddball condition, a deviant stimulus /ga/ or /ba/ (probability 1:12 for each) was rarely and randomly interspersed between frequently presented standard stimulus /da/ (probability 10:12). In an equiprobable condition, 12 syllables, including /da/, /ga/, and /ba/, were presented in a random order (probability 1:12 for each). We found evoked responses of higher amplitude to the deviant /ba/, albeit not to /ga/, relative to the standard /da/ in the oddball condition. Furthermore, the responses to /ba/ were higher in amplitude in the oddball condition than in the equiprobable condition. The findings suggest that anesthetized rat’s brain can form representations of human speech sounds, and that these representations can support the memory-based change detection mechanism analogous to that underlying the MMN in humans. Our findings show a striking parallel in speech processing between humans and rodents and may thus pave the way for feasible animal models of memory-based change detection.peerReviewe

Regulation of extracellular serotonin levels and brain-derived neurotrophic factor in rats with high and low exploratory activity

Serotonin (5-HT) system has a significant role in anxiety- and depression-related states and may be influenced by brain-derived neurotrophic factor (BDNF). This study examined extracellular 5-HT levels and expression of BDNF in rats with persistently low or high levels of exploratory activity (LE and HE, respectively). Baseline extracellular levels of 5-HT as assessed by in vivo microdialysis in conscious animals were similar in both groups in medial prefrontal cortex (PFC) and dentate gyrus (DG). No differences were found in parachloroamphetamine-induced 5-HT release in either region. However, LE animals had significantly higher levels of 5-HT transporter (5-HTT) binding in PFC and a larger increase in extracellular 5-HT levels after administration of citalopram (1 μM) into this area by retrograde dialysis. No difference in 5-HTT levels was found in hippocampus, while perfusion with citalopram was accompanied by a greater increase in extracellular 5-HT in the HE group in this brain region. LE-rats had higher levels of BDNF mRNA in the PFC but not hippocampus. In contrast, levels of nerve growth factor mRNA were similar in these brain regions of LE- and HE-rats. The differential regulation of 5-HT-ergic system in LE- and HE-rats in PFC and hippocampus may form the basis for their distinct anxiety-related behaviours