Ontogeny of septohippocampal modulation of delay eyeblink conditioning

Abstract

The current study investigated the effects of disrupting the septohippocampal theta system on the developmental emergence of delay eyeblink conditioning. Theta oscillations are defined as electroencephalographic (EEG) waveforms with a frequency between 3–8 Hz. Hippocampal theta oscillations are generated by inputs from the entorhinal cortex and the medial septum. Theta activity has been shown to facilitate learning in a variety of paradigms, including delay eyeblink conditioning. Lesions of the medial septum disrupt theta activity and slow the rate at which delay eyeblink conditioning is learned (Berry & Thompson, 1979). The role of the septohippocampal theta system in the ontogeny of eyeblink conditioning has not been examined. In the current study, infant rats received an electrolytic lesion of the medial septum on postnatal day (P)12. Rats were later given eyeblink conditioning for 6 sessions with an auditory conditioned stimulus on P17–P19, P21–23, or P24–P26. Lesions impaired eyeblink conditioning on P21–23 and P24–26 but not on P17–19. The results suggest that the septohippocampal system comes online to facilitate acquisition of eyeblink conditioning between P19 and P21. Developmental changes in septohippocampal modulation of the cerebellum may play a significant role in the ontogeny of eyeblink conditioning.

Developmental Changes in Hippocampal CA1 Single Neuron Firing and Theta Activity during Associative Learning

“…Post-hoc pairwise comparisons showed that CR peak latency in the two older age groups significantly differed from the P17-19 group during S2-3 as well as S4-5 ( p s < 0.05) ( Fig 3B ). Overall, the observed changes in eyelid EMG activity were similar to those seen in previous studies [ 32 , 34 ].…”

“…Eyeblink conditioning becomes progressively stronger between P17 and P24 in rats [ 32 , 33 ], and therefore develops during the period in which spatial memory and context conditioning develop. A previous study found that lesions of the medial septum impair acquisition of eyeblink conditioning in rat pups trained on P21-23 or P24-26, but not in pups trained on P17-19, suggesting that septohippocampal modulation of eyeblink conditioning emerges ontogenetically between P19 and P21 [ 34 ]. However, another study suggested that hippocampal function in associative learning might continue to develop past P21 [ 35 ].…”

Postnatal development of the relaxin-3 innervation of the rat medial septum

“…In support of this idea, septal lesions made at P12 impaired eye blink conditioning on P21–23, but not on P17–19 ( Harmon and Freeman, 2015 ). These results led the authors to postulate that the septohippocampal system and its subsequent control of hippocampal theta rhythm was active and able to facilitate eye blink conditioning between P19 and P21 ( Harmon and Freeman, 2015 ). Others have highlighted the relevance of this time window in the ontogeny of hippocampal theta rhythm, as rhythmic activity of inhibitory postsynaptic currents at theta frequencies first appears between P16 and P25, and these currents are disrupted by the activation of presynaptic GABA B receptors by the GABA B receptor agonist, baclofen ( Henderson and Jones, 2005 ).…”

“…In parallel to RXFP3 expression and the developmental appearance of RLN3 fibers between P15 and P17, immunohistochemical detection of Syn and its relative level of co-localization with RLN3 indicate that 'synaptic machinery' within the ascending RLN3 inputs develops later than P17 and that the NI to MS projection becomes functional after the maturation of the innervation. In support of this idea, septal lesions made at P12 impaired eye blink conditioning on P21-23, but not on P17-19 (Harmon and Freeman, 2015). These results led the authors to postulate that the septohippocampal system and its subsequent control of hippocampal theta rhythm was active and able to facilitate eye blink conditioning between P19 and P21 (Harmon and Freeman, 2015).…”