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A series of cell types will be presented in this Note that are not topographically organized, but rather geometrically organized. For example, grid cells are organized in a hexagonal grid in the entorhinal cortex, but do not topographically represent the information they encode.

Development

• Ensembles of place cells are formed both by experience as well as pre-determination
• New & stable place fields are dependent on behavior and attention to spatial features of the environment
• Some place cells show stable firing fields immediately while others develop over time as information is processed
• Place cells could be generated by:
  • Transformation of spatial input from grid cells
    • Patterns of grid cells cancel each other out except for central peak — becomes place field
  • But there’s delayed maturation of place cells (place cells are developed prior to grid cells)
    • Weak spatial inputs may be sufficient for place cell formation
    • Sharply confined firing fields generated by local mechanisms in hippocampal network (recurrent inhibition, active dendritic properties)
    • Or generated from other classes of spatially modulated cells like border cells (which have adult-like properties from first day of exploration outside nest)
  • Border cells may still linearly combine to produce place cells though (may be limited to place cells with peripheral firing fields)

Skeletal maps

• Skeletal maps of a novel environment are drawn from a set of preexisting maps and are modified to fit specifics of environment through experience-dependent plasticity

Plasticity

• Blockade of NMDA receptors and knockouts of those receptors do not have a large effect on basic firing patterns of place cells in either familiar or novel environments
  • Place-field expression is independent of at least one major form of long-term synaptic plasticity
  • Place-cell maps of the environment are stored & stabilized through changes in synaptic weights (similar to other memory systems)
• Selective attention, not general arousal, is a major determinant of experience-dependent stabilization of hippocampal place maps
  • Development of temporal coherence between activity in hippocampus and entorhinal cortex may allow CA1 cells to respond to particular entorhinal inputs at same time as cells are close to firing threshold

Asymmetric expansion

• Cells encoding for three separate locations that are visited in sequence experience inter-field synaptic strengthening, dependent on NMDA receptor activation and occurring through experience-dependent plasticity

Consolidation & Retrieval

Cell Types

Place Cells

• Discovered by John O’Keefe and John Dostrovsky (1971)
• Located in the hippocampus
• Likely receive input from both grid and border cells (grid — self-motion-based distance information, border — position in relation to geometric boundaries)
  • Grid cells are several times more abundant and likely have a larger contribution
• Encodes present location as well as context (what events take place or took place there)
  • Respond specifically to current location of an animal (and past location, and what location they should be in)
  • Place cells fire when animals make mistakes (as if the animal was in the location where the cell fires normally)
  • Different place cells have different firing locations or place fields
• Not topographically organized
  • Place fields of neighboring cells are no more similar than those of cells that are far apart
  • Rather, cells are organized by context and are associated based on connections between the encoded information
• Sequences of spatial firing are replayed during rest/sleep as if the patterns stored are consolidated during “offline mode”
• Earlier parts of hippocampal excitatory circuit (dentate gyrus & CA3) are not required for formation of place cells in CA1
  • Direct inputs from entorhinal cortex are an alternative source of incoming spatial information to the hippocampus

Remapping

• Place cells can alter firing patterns in response to minor changes in an experimental task
• New map is installed for each occasion
• Can be induced by changes in motivation
• Maps for different conditions/places usually completely uncorrelated: pattern-separation process may take place when info enters the Hippocampus from surrounding cortex.
• Remapping is likely initiated in the entorhinal cortex
  • Changes in environment leading to hippocampal remapping induce changes in firing locations of simultaneously recorded grid cells, but these changes are always coherent among numbers of grid cells.
    • Internal coherence is also seen with head-direction and border cells.
  • Two major explanations
    1. Continuous map of space in medial entorhinal cortex (different portions of which are activated in each environment)
    2. Grid cells have a modular organization and different modules react independently to changes in the environment
       • Differential realignment leads to different overlap of incoming grid signals in hippocampal target cells — the subset activated by entorhinal grid-cell inputs would be dependent on difference in realignment b/w diff modules
       • Studies have shown evidence for this!
         • Up to four modules
           • Four or fewer modules are sufficient to generate complete or global remapping in the hippocampus (computational model)
         • Modules respond with different degrees of displacement & re-orientation when animals move from one environment to another

Grid Cells

• Medial entorhinal cortex
• Sharply modulated by position as place cells in hippocampus
  • Multiple firing fields with clear silence between fields
• Provide input to place cells
• Firing fields of individual entorhinal neurons form a regularly spaced triangular or hexagonal grid pattern which repeats itself across available space
• Scale of grid increases from dorsal to ventral medial entorhinal cortex

Other types

Border cells

• Fire specifically along one or several borders of the local environment
• Subiculum

Head direction cells

• Obvious, respond to head direction

Interactions

• Whether entorhinal and hippocampal neurons influence each other depends on the state of theta and gamma oscillations (predominate frequency spectra in both regions during active awake behavior)