Modulation of hippocampal theta oscillations via deep brain stimulation of the parietal cortex depends on cognitive state.

The angular gyrus (AG) and posterior cingulate cortex (PCC) demonstrate extensive structural and functional connectivity with the hippocampus and other core recollection network regions. Consequently, recent studies have explored neuromodulation targeting these and other regions as a potential strategy for restoring function in memory disorders such as Alzheimer's Disease. However, determining the optimal approach for neuromodulatory devices requires understanding how parameters like selected stimulation site, cognitive state during modulation, and stimulation duration influence the effects of deep brain stimulation (DBS) on electrophysiological features relevant to episodic memory. We report experimental data examining the effects of high-frequency stimulation delivered to the AG or PCC on hippocampal theta oscillations during the memory encoding (study) or retrieval (test) phases of an episodic memory task. Results showed selective enhancement of anterior hippocampal slow theta oscillations with stimulation of the AG preferentially during memory retrieval. Conversely, stimulation of the PCC attenuated slow theta oscillations. We did not observe significant behavioral effects in this (open-loop) stimulation experiment, suggesting that neuromodulation strategies targeting episodic memory performance may require more temporally precise stimulation approaches.

A mouse model of stress-enhanced fear learning demonstrates extinction-sensitive and extinction-resistant effects of footshock stress.

Stressful experiences can cause long-lasting sensitization of fear and anxiety that extends beyond the circumstances of the initial trauma. The neural mechanisms of these stress effects have been studied extensively in rats using the stress-enhanced fear learning (SEFL) paradigm, in which exposure to footshock stress potentiates subsequent fear conditioning. Here we establish a mouse version of the SEFL paradigm. Male and female 129s6 mice received four 1-mA footshocks or equivalent context exposure without shock. Shock exposure induced Pavlovian fear conditioning to the shock context and produced three more general effects: (1) suppression of open field exploration, (2) potentiated unconditioned fear of a novel tone stimulus, and (3) enhanced fear conditioning in a novel context. To determine whether these effects of footshock stress reflect generalized Pavlovian fear conditioning versus nonassociative fear sensitization, some mice received extinction training in the footshock stress context, which reduced contextual fear to the levels of unstressed control mice. Extinction restored normal open field exploration, suggesting that this effect of stress reflects generalized Pavlovian fear. In contrast, extinction failed to attenuate stress-enhanced fear, indicating that stress-enhanced fear is nonassociative and mechanistically distinct from Pavlovian fear conditioning. The effects of footshock stress were similar in male and female mice, although female mice displayed larger acute responses to fear-inducing stimuli than did males. The results demonstrate that footshock stress influences emotional behavior through distinct associative and nonassociative mechanisms, which likely involve unique neural underpinnings.