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Bilateral 6-OHDA lesions of the locus coeruleus impair associative olfactory learning in newborn rats
R M Sullivan1, D A Wilson, C Lemon
1Department of Psychology, University of Oklahoma, Norman 73019.
Insights
Norepinephrine (NE) from the locus coeruleus is vital for early olfactory learning in rats. Lesions impairing NE reduced the ability of young rats to learn odor preferences.
Area of Science:
- Neuroscience
- Developmental Biology
- Behavioral Science
Background:
- The locus coeruleus is a key brainstem nucleus involved in neuromodulation.
- Early life experiences shape olfactory learning and memory development.
- Norepinephrine (NE) plays a crucial role in attention and learning.
Purpose of the Study:
- To investigate the role of norepinephrine (NE) from the locus coeruleus in early olfactory learning.
- To determine if NE depletion affects the acquisition of conditioned odor preferences in neonatal rats.
Main Methods:
- Wistar rat pups underwent bilateral 6-OHDA infusions into the locus coeruleus or received vehicle infusions on postnatal day 4.
- Pups were trained using a classical conditioning paradigm with citral odor (CS) and milk (UCS) on postnatal day 6.
- Acquisition of learned odor preference was assessed on postnatal day 7 using a two-odor choice test.
- High-performance liquid chromatography (HPLC) was used to measure neurotransmitter levels in the olfactory bulb.
Main Results:
- Locus coeruleus lesions significantly reduced NE content in the olfactory bulb but did not affect dopamine (DA) or serotonin (5-HT) levels.
- Lesioned pups showed no behavioral differences during training compared to controls.
- Acquisition of conditioned odor preferences was significantly impaired in pups with locus coeruleus lesions.
Conclusions:
- Norepinephrine output from the locus coeruleus is critical for the development of early olfactory learning.
- These findings highlight the importance of the locus coeruleus-norepinephrine system in mediating olfactory associative learning during early development.
Abstract:
On postnatal day 4 (PN4) Wistar rat pups were anesthetized and received bilateral infusions of 6-OHDA into the locus coeruleus or received vehicle infusions. On PN6 pups were trained in a classical conditioning paradigm with intra-oral milk infusions as the UCS and citral odor as the CS. Pups were trained in either 'paired', 'odor-only', 'milk-only' or 'backward' (milk then odor) conditions. On PN7 acquisition of a learned odor preference to the CS was tested in a two-odor choice test. HPLC analysis showed that locus coeruleus lesions significantly reduced olfactory bulb NE content but had no effect on olfactory bulb DA or 5-HT levels compared to controls. Pups receiving locus coeruleus lesions did not differ in behavioral response patterns during training compared to their littermate, vehicle controls. However, locus coeruleus lesions impaired acquisition of conditioned odor preferences. These results suggest that NE output from the locus coeruleus is critical for early olfactory learning.