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Intra ventral tegmental area noradrenergic receptor signalling regulates CUE-induced fear memory retrieval

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Zajda K., Drwiega G., Wira P., Szklarczyk K., Solecki W. B.

Acta Neurobiologiae Experimentalis

2019

tom 79

nr Suppl.1

INTRODUCTION: Noradrenergic receptors (α‑AR) in the ventral tegmental area (VTA) regulate phasic dopamine release in the mesolimbic, but not in the mesocortical pathway. Accordingly, the α‑ARs modulate conditioned behaviours, such as acquisition of fear memories. Importantly, the role of the VTA noradrenergic signaling in fear memory retrieval remain unclear. AIM(S): The aim of the study was to investigate the role of α1‑AR and α2-AR in VTA in the retrieval of conditioned stimulus (CS)‑induced fear memories. In control studies, we investigate their role in the locomotor activity and anxiety‑like behaviour. METHOD(S): We performed fear conditioning and open field tests in adult male, Spraque‑Dawley rats combined with intra‑VTA microinfusions. The fear conditioning consisted of two phases: training during which CS was associated with footshock, and retrieval of the conditioned fear memory. Retrieval test was preceded by intra‑VTA administration of α1‑AR and α2-AR antagonist (terazosin 1 µg/side and RX 821002 2.7 µg/side) and conducted in a novel context in which presentation of CS induced fear responses. RESULTS: We demonstrated that α1-AR blockade in the VTA decreased freezing responses during retrieval of CS‑induced fear memory. In contrast, α2AR blockade had no effects. Furthermore, neither blockade of α1-AR and α2-AR had no effects on locomotor activity and anxiety‑like behavior. CONCLUSIONS: Here, we demonstrated a potential role of the VTA noradrenergic signaling in fear memory retrieval. These results indicate that the noradrenergic signalling in the VTA modulates CS-fear induced responses predominantly via α1‑AR.

Characteristics of rat ventral tegmental area GABAergic-like neuronal responses to an aversive stimulus

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Drwiega G., Walczak M., Pradel K., Izowit G., Solecki W. B., Blasiak T.

Acta Neurobiologiae Experimentalis

2019

tom 79

nr Suppl.1

INTRODUCTION: The ventral tegmental area (VTA) is a major source of dopamine in the mammalian brain. Previous studies have confirmed that the pattern of VTA dopamine (DA) cell spontaneous activity is tonic rather than phasic during an activation state in contrast to deactivation (SWA), generated by urethane anesthesia. However, little is known about the second largest neuronal population in the VTA – GABA-ergic cells, which best known functional role is to inhibit the surrounding DA neurons, for e.g., in response to an aversive stimulus. AIM(S): The aim of our study was to investigate how VTA non-DA neurons respond to an aversive stimulus (footshock) and whether this reaction changes with an alterations in the brain states elicited by urethane anesthesia application. METHOD(S): We performed extracellular in vivo recordings of non-DA neurons combined with simultaneous recording of local field potentials from the hippocampus. Recordings were performed using SD‑TH‑Cre+/‑ rats under urethane anesthesia and electric footshocks were applied (45 per state) to the hindpaw of the animal in both brain states. We used optogenetics to identify the phenotype (DA vs. non-DA cell phenotype) of the footshock responsive cells by photo‑tagging. RESULTS: GABAergic-like (non-DA) cells respond to the footshock with either excitation (36%) or inhibition (16%) of their activity regardless of the brain states. Interestingly, a fraction of those non‑DA cells (20%) reacted with inhibition during activation and excitation during a deactivation state. The rest of the cells react with no‑responses in at least one state (28%). CONCLUSIONS: In line with previous studies, we observed a population of non-DA cells that react with excitation in response to footshocks. Interestingly, we also observed non-DA cells that were inhibited and populations that reacts depending on current brain state. Our results indicate a more complex role of GABAergic cells in response to footshock than previously assumed.

Ograniczanie wyników

2 Acta Neurobiologiae Experimentalis

2 Drwiega G.

2 Solecki W. B.

1 Blasiak T.

1 Izowit G.

1 Pradel K.

1 Szklarczyk K.

1 Walczak M.

1 Wira P.

1 Zajda K.

2 2019

Wyniki wyszukiwania

Intra ventral tegmental area noradrenergic receptor signalling regulates CUE-induced fear memory retrieval

Characteristics of rat ventral tegmental area GABAergic-like neuronal responses to an aversive stimulus