Two Roles of Hippocampus
Two research traditions provide very different accounts of hippocampal function:
- Cognitive Account: The hippocampus has been linked to spatial navigation (reviewed here) and declarative memory.
- Emotional Account: The hippocampus has been linked to the behavioral inhibition system, and its correlate – anxiety.
This situation is exacerbated by the radical simplicity of hippocampal circuitry. Buzsaki & Tingley (2018) attempt to unify the cognitive account, by exploring equivalencies between memory and navigation (both rely on sequential representations, with memory as “internal navigation at an attention-derived velocity”). But the cognitive and emotional strands are more difficult to reconcile. Strange et al (2014) attributes cognitive function to dorsal, and emotional function to ventral hippocampus. And there is strong lesion evidence in rats (Bannerman et al 2004) and neuroimaging studies in humans to support this view. It has a grain of truth.
But theta oscillations are found throughout the dorso-ventral axis. Yet these accounts attribute both emotional and cognitive properties to theta. This is puzzling. Is it reasonable to expect anxiety to lessen if running speed is reduced?
Varieties of Theta
Korotkova et al (2017) adduce evidence that cognitive and emotional elements contribute to the slope and y-intercept of theta, respectively. This dissociation was predicted by the Burgess (2008) model, which received empirical support in Wells et al (2013). These separate contributions to theta also cohere with developmental measures: large changes in intercept occurring between day 18 and 24 of the rat, despite much slower, gradual changes in slope (Wills et al., 2010).
But theta is not unitary. More precisely, the theta frequency band contains more than one oscillator. In rats, rabbit, and guinea pigs, two types of theta have been identified (Sainsbury & Montoya 1983). We recently found both oscillators in human neurosurgery patients (Goyal et al 2020), with very similar functional properties.
- Type 1 Theta (~9 Hz in rats, ~8 Hz in humans). Correlates with movement speed, and dependent on entorhinal cortex
- Type 2 Theta (~6 Hz in rats, ~3 Hz in humans). Does not correlate with movement speed.
The Respiration Oscillator
Theta is not the only biomarker relevant to behavioral inhibition. The hippocampus is also home to another rhythm entrained to breathing (Tort et al 2018). This respiration oscillator has been found in rat hippocampus (Lockmann et al 2016), and respiration-locked activity has been found in human cortex (Perl et al 2019). Beta oscillators peak at inspiration onset (Kluger & Gross 2021), which may explain why most voluntary behaviors are also initiated during this phase (Park et al 2020). Importantly, slow breathing promotes parasympathetic activity, mitigating the sympathetic arousal associated with BIS anxiety. This may mediate the health benefits provided by breath-centric meditation.
The nucleus incertus is one of four nuclei known to modulate theta rhythms, and it preferentially projects to the ventral hippocampus (Ma & Gundlach 2015). Within this nucleus, relaxin-3-positive neurons can be excited by the stress hormone corticotropin releasing factor (CRF) (Ma et al 2013). This constitutes a direct link between the stress response and hippocampal theta. This neuronal population also participates in respiratory activity (Furuya et al 2020), which strikes me as suggestive.
- Bannerman et al (2004). Regional dissociations within the hippocampus–memory and anxiety
- Burgess (2008). Grid cells and theta as oscillatory interference: theory and predictions
- Buzsaki & Tingley (2018). Space and time: the hippocampus as a sequence generator
- Furuya et al (2020). Relaxin-3 receptor (RXFP3) mediated modulation of central respiratory activity
- Goyal et al (2020). Functionally distinct high and low theta oscillations in the human hippocampus
- Kluger & Gross (2021). Respiration modulates oscillatory neural network activity at rest
- Korotkova et al (2017). Reconciling the different faces of hippocampal theta: the role of theta oscillations in cognitive, emotional and innate behaviors
- Lockmann et al (2016). A Respiration-Coupled Rhythm in the Rat Hippocampus Independent of Theta and Slow Oscillations
- Ma et al (2013). Heterogeneous responses of nucleus incertus neurons to corticotrophin-releasing factor and coherent activity with hippocampal theta rhythm in the rat.
- Ma & Gundlach (2015). Ascending control of arousal and motivation: role of nucleus incertus and its peptide neuromodulators in beharioral responses to stress
- Park et al (2020). Breathing is coupled with voluntary action and the cortical readiness potential
- Sainsbury & Montoya (1983). The relationship between type 2 theta and behavior
- Strange et al (2014). Functional organization of the hippocampal longitudinal axis
- Tort et al (2018). Respiration-entrained brain rhythms are global but often overlooked
- Wells et al (2013). Novelty and anxiolytic drugs dissociate two components of hippocampal theta in behaving rats.
- Wills et al (2010). Development of the hippocampal cognitive map in preweanling rats