Dendritic mechanisms of hippocampal place field formation

Abstract

Place cells in the hippocampus are thought to form a cognitive map of space and a memory of places. How this map forms when animals are exposed to novel environments has been the subject of a great deal of research. Numerous technical advances over the past decade greatly increased our understanding of the precise mechanisms underlying place field formation. In particular, it is now possible to connect cellular and circuit mechanisms of integration, firing, and plasticity discovered in brain slices, to processes taking place in vivo as animals learn and encode novel environments. Here, we focus on recent results and describe the dendritic mechanisms most likely responsible for the formation of place fields. We also discuss key open questions that are likely to be answered in the coming years.

Figure 1.

Hippocampal place field formation at the ensemble level and active dendritic signaling in CA1 pyramidal neurons. (a) Switching from a familiar to a novel environment causes global remapping of CA1 place fields (colored neurons indicate place cells). CA1 neurons in the novel environment can either be silent (no place field), form a place field after some time or experience (delayed place field), or form a place field immediately (instant place field). (b) CA1 pyramidal neurons receive input from CA2 and CA3 on their basal and proximal apical dendrites, and entorhinal layer 3 cortical inputs on their tuft dendrites (Left). These inputs can cause a number of postsynaptic responses (from left to right): local NMDA spikes in basal, oblique apical, and tuft dendrites in the absence (or presence, not shown) of somatic AP firing; Somatic firing without any branch spiking in the dendrites; Somatic firing with bAPs that cause global branch spiking in the dendrites; Somatic burst firing with co-occurring plateau potential generated in the distal apical dendrite that causes global branch spiking (calcium spike). These distinct responses are shown in isolation, but combinations of these can also co-occur. EC: Entorhinal cortex. EC3: Entorhinal cortex layer 3. DG: Dentate gyrus. bAPs: backpropogating action potentials.

Figure 2.

Dendritic mechanisms of instant place field formation, precision, and stability. The top box shows two possible modes of somatic firing and co-occurring dendritic branch spiking during the first traversal of this cell’s place field in a novel environment (instant place field). The mechanism driving instant place field firing is through activation of pre-strengthened pathways (red and black spines) that are sufficient to cause somatic firing. If the cell fires in burst mode, it can lead to behavioral timescale synaptic plasticity, although this is not necessary for place field firing on subsequent laps. The bottom box depicts the average branch spike prevalence that could occur across the dendritic arbor over many traversals of a cell’s place field once the environment has become familiar; 3 different example cells are shown. A low average branch spike prevalence is associated with place fields that are imprecise and lack stability, i.e. they tend to disappear over time, and vice versa.

Figure 3.

Dendritic mechanisms of delayed place field formation, precision, and stability. The top 2 boxes depict CA1 pyramidal cells that initially lack place fields during the first few traversals of a novel environment. In one case (top left box), clustered synaptic input at 5 locations across the arbor generates 5 local NMDA spikes. This occurs at a particular spatial location in the animal’s environment. The clustered and co-activated synapses that caused the NMDA spikes become potentiated. On subsequent traversals of that location in the environment, reactivation of the same inputs is now sufficient to drive somatic firing (either regular or burst firing), causing a delayed place field to appear. The next steps are the same as those described in Figure 2. In the other case (top right box), the initially silent neuron forms a delayed place field through a change in the activation of inputs onto the neuron. This could occur through changes in attention associated with specific behaviors like head-scanning. The subsequent steps leading to place field formation depend on the pattern of inputs, and could either require no synaptic plasticity (left middle box) or could generate local NMDA spikes that cause synaptic plasticity (top left box).

Figure 4.

Possible scenarios that prevent place field formation. The top 2 boxes show somatically silent CA1 pyramidal neurons during the first traversal of a novel environment. In both cases, there is no development of a delayed place field on subsequent traversals of the environment. The failure to form a place field could be due to weak inputs that fail to drive the cell to fire and also fail to generate local NMDA spikes, so no synaptic strengthening takes place (top right box). Alternatively, input is sufficient to cause some NMDA spikes, but there is an insufficient number of these events across the dendritic arbor to cause enough synaptic potentiation to drive subsequent place field firing at the soma. This scenario would also occur if the neuron produced the same frequency of NMDA spikes as delayed onset place fields, but the spikes occurred at various environment locations, with insufficient numbers of overlapping spikes at one particular environment location.