Revisiting the Hippocampus Place Cells and Head-direction Cells Study Guide

Navigation and the Role of the Hippocampus in Humans and Animals

• Introduction to Hippocampal Function: Building on previous knowledge, lesions of the hippocampus lead to significant navigational impairment.

• Human Hippocampal Plasticity (VBM Study):

  • Research using adjusted Voxel-Based Morphometry (VBM) responses identifies significant density changes in the posterior hippocampus of human subjects.

  • London Taxi Driver Study:

    • Evidence shows a positive correlation between the time spent as a taxi driver (measured in months) and the volume of the posterior hippocampus.

    • Data points for time as a taxi driver range from $0$ to over $400$ months.

    • Comparison of route recall versus landmark recall shows peak activation in the right hippocampus (identified at coordinates involving $z = -8\,mm$, $z = -6\,mm$, and $z = -4\,mm$).

    • Significant activations during route recall were also observed in the medial parietal region and the posterior cingulate gyrus.

• Comparative Navigation in Birds:

  • Homing Behavior: Birds also possess a hippocampus. Studies by Bingman et al. ($2005$) show that hippocampal-lesioned birds exhibit impaired homing abilities compared to controls.

  • Examples of homing distances recorded include $13.6\,km$ and $19.0\,km$.

  • Food Storing Behavior: Comparative studies by Sherry & Healy ($1985$) demonstrate structural differences based on evolutionary niche:

    • Food storers (average weight $11\,g$) have a hippocampal volume of $14.42\,mm^3$.

    • Non-food storers (average weight $20\,g$) have a hippocampal volume of $11.2\,mm^3$.

    • This represents a $31\%$ increase in hippocampal volume for food storers regardless of smaller body mass.

Place Cells and Their Behavioral Characteristics

• Definition of Place Cells: These cells fire specifically and solely as a result of an animal's location within a given environment.

• Stability and Memory:

  • Place cells remain stable for long periods of time.

  • They continue to fire in the dark, suggesting a strong memory component or reliance on internal cues rather than just immediate visual input.

• Environmental Coverage:

  • When recording from a population of cells, the entire environment is covered.

  • Different cells become active in different locations.

  • As few as $32$ neurons are sufficient to cover an entire square environment.

• Predictive Firing and Intent:

  • Firing rates of place cells can predict where an animal is going to go. This indicates a link between neural change and behavioral change.

  • Wood et al. (2000): Study on "splitter cells" in T-maze tasks show different firing patterns for left-turn trials versus right-turn trials across different sectors of the maze.

  • Ainge et al. (2007): Research published in The Journal of Neuroscience ($27(36):9769-9779$) demonstrate that place cells at the start box encode the intended direction of the animal.

Head-Direction (HD) Cells and Neural Circuitry

• Definition of Head-Direction Cells: These cells represent the animal's heading. A single HD cell fires only when the animal's head is pointed in its "preferred direction."

• Standard Characteristics:

  • These cells are found in both rats and monkeys.

  • They fire independent of the animal's location, focusing only on orientation/azimuth.

  • The firing rate is typically represented in a circular plot (e.g., $0^{\circ}$, $90^{\circ}$, $180^{\circ}$, $270^{\circ}$, $360^{\circ}$).

• Reliance on Visual Landmarks:

  • HD cells rely on visual landmarks for orientation.

  • Rotation of a visual cue in the environment leads to a concurrent rotation in the firing direction of the HD cells.

• Anatomical Circuitry of the HD System:

  • Vestibular Nuclei $\rightarrow$ Lateral mammillary nucleus $\rightarrow$ Anterior thalamus / Lateral dorsal thalamus $\rightarrow$ Post-subiculum / Retrosplenial Cortex.

  • This hierarchy eventually influences the Entorhinal Cortex (EC) and the hippocampus (CA1, CA3, DG).

Grid Cells and the Medial Entorhinal Cortex (mEC)

• Discovery of Grid Cells: Discovered in $2005$ by Hafting, Fyhn, Molden, and the Mosers in the Medial Entorhinal Cortex (mEC).

• Firing Properties:

  • Unlike place cells which fire in one location, grid cells fire at multiple locations that form a regular hexagonal lattice or "grid" across the environment.

  • Firing frequencies recorded include levels such as $6\,Hz$, $7\,Hz$, $9\,Hz$, $11\,Hz$, $15\,Hz$, and $19\,Hz$.

• Dynamic Responses:

  • Cue Rotation: Grid cells rotate their orientation in response to the rotation of visual cues.

  • Persistence in Darkness: Like place cells, grid cells persist in the dark (recorded at $16\,Hz$ in light vs. $9\,Hz$ in dark in some instances).

  • Rapid Development: Grid cells develop quickly when an animal enters a new environment.

• Topographic Organization:

  • As one moves from the dorsal (top) to the ventral (bottom) mEC, the distance between the peaks of the grid increases.

  • The relationship between dorsoventral location ($m$) and peak distance is characterized by an $R^2 = 0.67$.

Spatial Navigation Cells in Humans

• Clinical Research Methodology: Studies by Ekstrom et al. (2003) and Jacobs et al. (2013) involved patients with drug-resistant epilepsy undergoing surgery with intracranial electrodes to identify seizure foci.

• Human Navigation Task: Subjects played a "taxi driver computer game" in a virtual town, searching for random passengers and delivering them to fixed locations.

• Cell Types in Humans:

  • Place-specific cells: Found in the hippocampus.

  • View-responsive cells: Found in the right parahippocampal cortex, responding to specific views (e.g., specific shops like "SA").

  • Grid-like Cells: Jacobs et al. ($2013$) recorded direct grid-like neuronal activity in the human entorhinal cortex. Approximately $14\%$ and $8\%$ of cells in specific recorded regions showed these properties.

  • Path Cells: These cells encode the direction of rotation or the path taken (e.g., Firing rate changes based on Clockwise (CW) vs. Counter-Clockwise (CCW) turns).

• fMRI Evidence for Grid Cells:

  • Doeller et al. (2010): Used fMRI to identify grid cell signatures in the entorhinal cortex of healthy humans.

  • Observed a specific hexagonal symmetry in the fMRI signal change ($\approx 0.5\%$) based on the alignment of the running direction with the grid axes ($\phi + 60^{\circ}$, $\phi + 120^{\circ}$, etc.).

Conclusions and Implications

• Cross-Species Importance: The hippocampus is vital for spatial navigation in both mammals and non-mammals.

• Functional Diversity: The system utilizes Place cells (location), HD cells (heading), and Grid cells (potentially distance or coordinate systems).

• Open Questions: There is still uncertainty regarding how grid cells specifically contribute to navigation (e.g., distance measuring) and why certain cells found in humans differ slightly from those in animal models.

Questions & Discussion

• What is the function of these cells?: It is hypothesized they contribute to distance representation or a coordinate system for navigation.

• Do humans have these cells?: Yes, evidence from intracranial recordings and fMRI suggests humans possess place, HD, grid-like, and "path" cells.

• How does firing relate to behavior?: Changes in firing rate (Hz) often precede or correlate with behavioral choices, such as turning direction in a maze.