The brain is impossibly complicated - if it were simple enough to understand, we'd be too simple to understand it. - Lyall Watson

Spatial representation “We live in it, move through it, explore it, defend it… yet we find it difficult to come to grips with space” (O’Keefe and Nadel, 1978). “We live in it, move through it, explore it, defend it… yet we find it difficult to come to grips with space” (O’Keefe and Nadel, 1978). Space is not a sensory modality (we do not have sensory organs for it – it is a construct of mental processing). Space is not a sensory modality (we do not have sensory organs for it – it is a construct of mental processing). Memory system – evolved in response to environmental demands. Memory system – evolved in response to environmental demands.

Bast, 2007

Intra-hippocampal anatomy/circuitry

Place cells Single neurons that fire when the rat moves through a specific location (O’Keefe and Dostrovsky, 1971). Single neurons that fire when the rat moves through a specific location (O’Keefe and Dostrovsky, 1971). –Pyramidal & Granule Area where a cell fires is its “place field”. Area where a cell fires is its “place field”. Still fire when landmarks removed, light turned off (Hafting et al., 2005). Still fire when landmarks removed, light turned off (Hafting et al., 2005). Most studies in environments about 1m across (small area for a rat) – this study uses an 18m track –larger spatial scales. Most studies in environments about 1m across (small area for a rat) – this study uses an 18m track –larger spatial scales.

Place cells Replay - Cells coactivated during awake behavior have correlated activity during sleep (consolidation?, Wilson and McNaughton, 1994). Replay - Cells coactivated during awake behavior have correlated activity during sleep (consolidation?, Wilson and McNaughton, 1994). Preplay - firing in a T-maze went ahead in the direction of reward location (Johnson and Redish, 2007). Preplay - firing in a T-maze went ahead in the direction of reward location (Johnson and Redish, 2007). –Retrieval of stored spatial representations. –Hippocampus – active problem solving.

Remapping Memory interference – similar memories. Memory interference – similar memories. Place fields can appear, disappear, or move randomly (seemingly). Place fields can appear, disappear, or move randomly (seemingly). –Rate remapping –Global remapping Depends upon differences in environment – memory separation. Depends upon differences in environment – memory separation.

Place cell plasticity Neves et al., 2008

Head-direction cells Neurons that fire when the animals head faces a specific direction in the horizontal plane. Neurons that fire when the animals head faces a specific direction in the horizontal plane. Independent of movement / behavior. Independent of movement / behavior. Vestibular input critical to direction signal. Vestibular input critical to direction signal.

Taube, 2008

Goal cells?

Grid cells Medial entorhinal cortex – multiple firing fields, forming a grid. Medial entorhinal cortex – multiple firing fields, forming a grid. Firing fields dispersed over the entire environment. Firing fields dispersed over the entire environment. Firing fields are generally equally spaced apart, distance from one firing field to all adjacent firing fields is approximately the same. Firing fields are generally equally spaced apart, distance from one firing field to all adjacent firing fields is approximately the same.

Place Cells – hippocampus. Place Cells – hippocampus. Head direction cells – presubiculum. Head direction cells – presubiculum. Grid – entorhinal cortex. Grid – entorhinal cortex. –Thalamus –Parietal cortex Cell types together provide info for a mapping system. Cell types together provide info for a mapping system. –Location, distance/direction between locations. Spatial representation system

Aims Ventral place cells? Ventral place cells? –How is space represented along the dorsoventral axis of the hippocampus?

Materials and methods Twenty-one male Long-Evans rats ~ g. Twenty-one male Long-Evans rats ~ g. Testing occurred in the dark phase. Testing occurred in the dark phase. Rats trained to run back and forth on an 18 m long and 12 cm wide linear track. Rats trained to run back and forth on an 18 m long and 12 cm wide linear track. Running maintained by chocolate crumbs at each of the turning points. On recording trials, the rats ran approximately 10 consecutive laps in each direction. Running maintained by chocolate crumbs at each of the turning points. On recording trials, the rats ran approximately 10 consecutive laps in each direction. On the 18 m track, the rat’s position was tracked by an eye- safe invisible laser beam placed at one end of the track. On the 18 m track, the rat’s position was tracked by an eye- safe invisible laser beam placed at one end of the track.

Materials and methods

The head stage was connected to a 10m long cable that moved freely. The head stage was connected to a 10m long cable that moved freely. An experimenter consistently followed 1 m behind the rat to ensure that there was no strain from the cable on the rat’s head. An experimenter consistently followed 1 m behind the rat to ensure that there was no strain from the cable on the rat’s head. The tetrodes were lowered in steps of 50 μm or less until single neurons could be isolated at appropriate depths. The tetrodes were lowered in steps of 50 μm or less until single neurons could be isolated at appropriate depths. After each recording, the tetrodes were moved further until new well-separated cells were encountered. The most ventral recording locations were encountered days after the start of tetrode turning. After each recording, the tetrodes were moved further until new well-separated cells were encountered. The most ventral recording locations were encountered days after the start of tetrode turning.

Materials and methods Histology. The rats were perfused (with electrodes in?). The rats were perfused (with electrodes in?). Sectioned (30  m) using a cryostat. Sectioned (30  m) using a cryostat. The positions of the tips of the recording electrodes were determined. The positions of the tips of the recording electrodes were determined.

Blue=CA3 Red=CA1 Purple=Subiculum

CA3 Place fields Left runs = “Red” Right runs = “green” Top = firing rate as function of position Bottom = spike density on individual laps

Most ventral = 5-10m place field

Theta phase precession Theta 4-12Hz oscillation, EEG. Theta 4-12Hz oscillation, EEG. Neuron fires in relation to theta cycle (0-360 degrees). Neuron fires in relation to theta cycle (0-360 degrees). As a rat moves through a place field the neuron fires earlier and earlier in the cycle. As a rat moves through a place field the neuron fires earlier and earlier in the cycle. Each place cell will fire at a different phase of theta - determining location with good precision and possibly providing temporal code. Each place cell will fire at a different phase of theta - determining location with good precision and possibly providing temporal code.

Theta phase precession dorsalIntermediateVentral

dorsal Intermediate Ventral Composite rate maps

Spatial scale as function of position along longitudinal axis of hippocampus

Conclusions Ventral place cells? – yes Ventral place cells? – yes Dorsal hippocampal neurons – mean of 98cm. Dorsal hippocampal neurons – mean of 98cm. Ventral hippocampal neurons (>10m). Ventral hippocampal neurons (>10m).

Conclusions Behavioral differences – dorsal / ventral hippocampus. Behavioral differences – dorsal / ventral hippocampus. –Smaller scales (watermaze) – Dorsal place fields. –Larger scale (contextual conditioning) – ventral place fields.  Fire everywhere in one room and nowhere in another.