The complexity of this is further compounded,

as directly investigating hetereosynaptic synergism and/or competition should optimally be performed in the intact brain where all of the functional connectivity is preserved. To tackle this, Calhoon and O’Donnell (2013) NVP-BKM120 in vivo performed sharp electrode recordings from VS MSNs in anesthetized rats while examining how electrical stimulation of the prefrontal cortex (PFC) altered MSN responses to electrical stimulation of either hippocampal input via the fimbria-fornix or thalamic input. Strong burst-like stimulation of the PFC, comparable to the firing patterns observed in some PFC neurons during behavioral tasks (Peters et al., 2005), produced subthreshold learn more depolarization in VS MSNs but rarely led to robust spiking. Surprisingly, when either fornix or thalamic stimulation was delivered immediately after PFC stimulation, instead of an expected summation of excitatory responses that produced even

more robust MSN activation, the responses induced by thalamic and hippocampal inputs were attenuated, suggesting that heterosynaptic competition may exist between VS excitatory synaptic inputs, analogous to phenomena seen in other brain regions (Fuentealba et al., 2004). Importantly, direct depolarization comparable in amplitude and duration to those induced by PFC stimulation did not Calpain attenuate hippocampal or thalamic MSN responses, suggesting that it is not depolarization

per se that can account for PFC-induced suppression of competing inputs. While a number of potential candidate cellular and circuit mechanisms exist that could account for an attenuation of hippocampal and thalamic input by PFC activation, one interesting possibility is that PFC innervation also activates inhibitory neurons within the VS, such as fast-spiking interneurons (FSIs). FSIs make up <1% of the neuronal composition of the VS (Luk and Sadikot, 2001) but have potent inhibitory network effects. In addition, VS FSIs show entrainment with cortical oscillations (Berke, 2009; Gruber et al., 2009a), suggesting direct or indirect functional connectivity between VS FSIs and PFC activity. To examine whether inhibitory processes, such as the activity of VS FSIs may regulate heterosynaptic suppression of hippocampal inputs by PFC stimulation, Calhoon and O’Donnell (2013) introduced open channel GABAA blockers intracellularly via sharp electrodes in some experiments. Blockade of GABAA receptors in VS MSNs produced greater excitation, including the induction of action potentials in response to PFC stimulation as well as reduced heterosynaptic suppression, suggesting that these processes were at least partially mediated by GABAA signaling onto MSNs. The activity of VS MSNs are often entrained to hippocampal activity (Berke et al.