Learning-facilitated long-term depression and long-term potentiation at mossy fiber—CA3 synapses requires activation of β-adrenergic receptors

Abstract

Learning-facilitated plasticity refers to hippocampal synaptic plasticity that is facilitated by novel spatial learning events. Both long-term potentiation (LTP) and long-term depression (LTD) are facilitated by novel hippocampus-dependent learning. This has important ramifications for our understanding of how the hippocampus encodes memory. One structure that is rarely studied in vivo, but is believed to be crucially important for working and long-term memory processing is the hippocampal CA3 region. Whereas learning-facilitated plasticity has been described in this structure, the mechanisms underlying this phenomenon have not been explored. The noradrenergic system plays an important role in arousal and qualification of new information as salient. It regulates synaptic plasticity in the dentate gyrus and CA1, but nothing is known about the regulation by the noradrenergic system of synaptic plasticity in the CA3 region. We explored whether β-adrenergic receptors contribute to learning-facilitated plasticity at mossy fiber (mf)-CA3 synapses of behaving rats. We found that receptor antagonism had no effect on basal synaptic transmission, short-term potentiation (STP), short-term depression, LTP, or LTD, that were electrically induced by patterned afferent stimulation. We found, however, that both learning-facilitated LTP and LTD were prevented by antagonism of β-adrenergic receptors, whereas the agonist isoproterenol facilitated STP into LTP. Thus, learning-facilitated and electrically-induced plasticity may not share the same prerequisites. These results support that the mf synapse engages in a distinct aspect of encoding of spatial information that involves both LTP and LTD. Furthermore, changes in arousal that are coupled to new learning are associated with activation of hippocampal β-adrenergic receptors that in turn comprise a key element in this type of information acquisition and processing by the CA3 region.

The temporoammonic input to the hippocampal CA1 region displays distinctly different synaptic plasticity compared to the Schaffer collateral input in vivo: significance for synaptic information processing

“…Our data support that synaptic plasticity at this synapse is distinct from the main synapses of the trisynaptic network: the thresholds for LTP induction are lower and LTP evoked at lower frequencies is more robust than LTP evoked at the Sc-CA1 synapse, (this study) or in pp-dentate gyrus, mossy fiber-CA3 or commissural associational synapses of the CA3 region in freely behaving rats (Manahan-Vaughan et al, 1998; Kemp and Manahan-Vaughan, 2008; Hagena and Manahan-Vaughan, 2012). LTD is induced at the isolated pp-CA1 synapses but appears to be subjected to a strong modulatory control by Sc-CA1 synapses under conditions where all hippocampal synapses are intact.…”

Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination

“…There is evidence for synergism between the β-adrenergic receptor agonist, isoproterenol, and repetitive synaptic stimulation of MF-LTP in slice culture (Huang and Kandel, 1996). More recently, it has been observed that a weak tetanic stimulation of the MF-CA3 pathway in vivo can synergize with lateral ventricle administration of isoproterenol to elicit LTP lasting more than 24 hr (Hagena and Manahan-Vaughan, 2012). In addition, the pituitary adenylate cyclase activating peptide (PACAP) receptor is highly expressed in DGCs and this Gs-coupled GPCR is localized to MF projections (Otto et al, 1999).…”

Synaptic depression in the CA1 region of freely behaving mice is highly dependent on afferent stimulation parameters

“…Furthermore, these data highlight important differences between rat and mouse hippocampal LTD. In rats in vivo , LTD of differing durations can be elicited by a wide range of protocols (Manahan-Vaughan, 2000a) and the range of protocols for LTP induction is even wider (Staubli and Lynch, 1987; Kemp and Manahan-Vaughan, 2004, 2008b; Neyman and Manahan-Vaughan, 2008; Hagena and Manahan-Vaughan, 2012). The intriguing finding that the spectrum of stimulation parameters for induction of synaptic depression in vitro is highly restricted is complemented by similar findings with regard to murine LTP in vivo (Buschler et al, 2012).…”