Ventral tegmental area modulation of hippocampal mnemonic functions

The integrity of hippocampus (HPC) is crucial for the ability to form new episodic memories. Spatial learning and context processing are likely components of episodic memory and HPC has been implicated in mediating these mnemonic functions on behavioral and neurophysiological levels. Place cells in HPC display location specific firing (place fields) and place field qualities are thought to underlie spatial memory and context discrimination. HPC dependent memory is also known for complex associative properties. Thus an accurate assessment of HPC memory should also account for relationships with a range of input structures. Dopamine (DA) is a neuromodulator that impacts HPC dependent behaviors and physiology. Furthermore, HPC indirectly projects to ventral tegmental area (VTA) DA neurons and is thought to impact DA neuron firing to regulate HPC dependent memory formation. Thus, HPC and VTA are thought to form a loop that facilitates the encoding of episodic memories.;HPC receives most of its DA input from VTA and although DA modulation of HPC mnemonic function has been investigated, few studies have examined the role of VTA in HPC processing. Therefore, VTA's contribution to spatial memory was examined along with its influence on HPC place fields. Temporary inactivation of DA activity in VTA was found to be detrimental for accurate performance on a context dependent spatial working memory task. Furthermore, disruptions of VTA DA activity produced deficits in mnemonic properties of place fields that are thought to underlie accurate spatial memory formation. The firing properties of DA neurons have been studied at length in relationship to classical conditioning paradigms and are thought to provide a neural substrate for reward prediction that facilitates learning. However, few studies have investigated VTA neural activity during HPC dependent behavioral tasks. Thus the specific relationships of VTA DA neuron activity in relation to acquisition of a HPC dependent spatial task were assessed. VTA neural activity was found to reflect learning navigational and mnemonic demands of the task and spatial properties of reward locations. Together the results from these experiments suggest a role for VTA in stabilizing HPC dependent neural and behavioral functions that process spatial representations of rewards.